Endocrine Abstracts

The central hypothyroidism (CeH) is a hypothyroid condition due to an insufficient stimulation by TSH of an otherwise normal thyroid gland. CeH is about 1000-fold rarer than primary hypothyroidism (PH). Differently to PH, the CeH is most frequently characterized by low/normal TSH levels and thyroid hormone replacement is associated with the suppression of residual TSH secretion even during low thyroxine regimen.Thus, CH management often represents a clin...

Primary ovarian failure (POF) is defined as a premature ovarian defect characterized by absent menarche (primary amenorrhea) or secondary amenorrhea lasting at least 6 months associated with a premature depletion of ovarian follicles before the age of 40 years. POF is a frequent disease affecting female fertility and well-being and generating several co-morbidities. Since the onset of POF is frequently silent and fertility defects occur in the occult phases of the disease seve...

Congenital hypothyroidism (CH) is the most frequent endocrine congenital defect affecting about 1:3000 newborns. In economically/ socially advanced counties, CH is routinely screened by means of TSH (and/or T4) measurement on dry blood spot (dbs) since more than 20 years. Neonatal screening allows early recognition and treatment of affected newborns. Upon data collected in years <2000 by the Italian CH Registry, the newborns with confirmed CH and gland-in-situ constituted ...

In clinical practice, most thyroid disease is due to thyroid gland dysfunction and so can be detected by measurement of TSH alone. This is because the negative feedback of thyroid hormones on the hypothalamus and pituitary gland result in TSH levels that are closely, and inversely, correlated with circulating free thyroid hormone (FT4, FT3) levels. However, several conditions are exceptions to this rule and can be very hard to diagnose also due to a certa...

Thyroid hormone action defects (THADs) are caused by the defective action of thyroid hormones (THs) through their receptors (TRs). TRs variants (TRα1 or TRβ) are associated with several defects, which depend mainly on the tissue-specific expression of the defective-receptor. One of the most striking manifestations is the deregulation of the hypothalamus–pituitary–thyroid axis (HPT); patients with TRα1-mutations show normal thyroid volume, low T4/T3 and...

Introduction: As in humans, thyroid hormone (TH) plays an essential role on zebrafish development by acting through the specific nuclear receptors (TRα or TRβ) and activating/suppressing the expression of several target genes. In zebrafish, TRα is preferentially expressed in the heart and CNS while the TRβ is mainly expressed in the retina and inner ear, but the specific role of these receptors in the different target tissues is presently unknown. In this s...

The pathogenesis of premature ovarian failure (POF) is largely unknown. However, the evidence of a frequent familiarity for the anticipation of menopause among POF women supports the concept of a strong genetic component at the origin of POF. This is further supported by the findings of several candidate genes and by data coming from natural and experimental animal models. On these bases, several groups are involved in the search for markers able to predict the risk of POF. Th...

Thyroid hormone receptors (TRs) modulate various physiological functions in many organs. The conservation of TRα and TRβ isoforms during evolution of vertebrates suggests different roles for these TRs in thyroid hormone-dependent regulation of gene expression. TRα and TRβ are widely distributed and overlapping in several tissues, and their functional divergence is mainly attributed to their variable tissue expression patterns and intrinsic properties of spe...

Anaemia in RTHα patients correlates with documented abnormal erythropoiesis and reduced haematocrit in TRα-null or mutant mice, but the underlying mechanisms and characterization of the defect remain elusive. In a previous work, we described that the injection of several hTRα variants in zebrafish eggs caused a marked reduction of circulating erythrocytes at later stages of the erythropoiesis. To characterise the involvement of TRα during erythrocyte develo...

Introduction: Since 2012, different heterozygous mutations in the THRA gene have been described in patients with resistance to thyroid hormone alpha (RTHα). The associating symptoms are reminiscent of untreated congenital hypothyroidism (growth retardation, psycho-neuromotor disorders, delayed bone development and bradycardia) but with raised T3/T4 ratio and normal TSH levels. All genetic abnormalities act in a dominant negative (DN) manner against functional rec...