Endocrine Abstracts

Thyroid cancer is the most common endocrine malignancy characterized by a good prognosis. However, the subgroup of poorly differentiated thyroid carcinomas (PDTCs) includes neoplasia highly aggressive and scarcely responsive to currently available therapies.Site-selective cAMP analogs are able to inhibit the growth of poorly differentiated solid tumors and may represent valuable candidates for the therapy of PDTCs.We evaluated the ...

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor highly resistant to chemo-and radiotherapy. Since several reports showed that cAMP has an antiproliferative effect on different types of solid tumors both in vitro and in vivo, we evaluated the potential anti-neoplastic activity of cAMP analogues (8-Cl-cAMP and the equimolar combination of 8-PIP-cAMP and 8-HA-cAMP) in two MTC cell lines (TT and MZ-CRC-1 that harbor C634W and M918T RET mutations, respecti...

Tools that are highly effective in the treatment of differentiated thyroid cancer (DTC) loose their therapeutic potentials in poorly differentiated tumors. The synthetic analog 8-Cl-cAMP has been known to have an antiproliferative effect in a variety of cancer cells and is tested as antineoplastic agent in clinical trials. The signaling mechanisms that govern the 8-Cl-cAMP-induced growth inhibition are still uncertain and data in thyroid neoplasia are lacking. Therefore, we te...

In thyroid cells TSH/cAMP stimulation is associated with proliferation and differentiation. The principal effector of cAMP is the protein kinase A (PKA) and events downstream PKA activation, signaling specificity and expression of PKA isoforms are largely unexplored. PKA is composed of two regulatory and two catalytic subunits. Two major isoforms of PKA (I and II) are determined by their specific regulatory subunits (RIα, RIβ, RIIα and RIIβ). A recent gene ...

Thyroid stimulating hormone (TSH) is the key modulator of thyroid cell function. Binding of TSH to its receptor (TSHR) results in an increase of cAMP intracellular concentration, which activates protein kinase A (PKA) to phosphorylate CREB and other substrates. Eventually, this leads to gene transcription modification associated with both proliferation and differentiation. Two major types of PKA (PKA I and II) exist in mammal cells, but their specific role in TSH signaling is ...

Congenital Hypothyroidism (CH) is the most common congenital endocrine disease and avoidable cause of severe mental retardation. The CH pathogenesis may include the contribution of genetic and environmental factors. However, causal mutations have been found in a minority of cases. Moreover, the elevated frequency of discordance for CH phenotype between monozygotic (MZ) twins suggests the involvement of non-Mendelian mechanisms. Aim of this study was to investigate the role of ...

Thyroid dysgenesis accounts for 75% of all cases of congenital hypothyroidism (CH), and includes thyroid agenesis or hemiagenesis, thyroid hypoplasia, and thyroid ectopy. Thyroid transcription factors TTF-1, TTF-2 and Pax-8, which are involved in the development of the thyroid gland and its normal migration, have been indicated as the best candidate genes but have been found to be mutated in a minority of cases. Sonic Hedgehog (Shh) protein is involved in several key events du...

Isolated central hypothyroidism (ICH) is a rare disease whose pathogenesis is so far linked to germinal mutations of TSHβ (several cases) or TRH receptor (TRHR) genes (only two cases). Here, we report the studies performed to elucidate the pathogenesis of idiopathic ICH in five cases (two men, three women) with low/normal TSH levels and low freeT4 levels (3–8 pmol/l). One male, negative at neonatal TSH screening, showed signs of severe hypothyroidism at 44...

Congenital hypothyroidism (CH) is frequently associated with congenital heart defects (CHD). Thyroid defects may have a higher prevalence in children with CHD as embryonic thyroid gland share nuclear transcription factors with heart and great vessels during organogenesis. We investigated thyroid function in 325 children (165 M/160 F, aged 0.2–15.4 years), affected by CHD. Patients with Down syndrome, recent administration of iodinated contrast agents, low T3 sy...

Mild hypothyroidism is a heterogeneous and frequent disorder in the general population that is due to autoimmune disease in most of the cases. TSH resistance is considered a rare genetic disease due to germline loss-of-function TSHR mutations. However, TSHR mutations have been mainly searched in patients with large TSH elevations and their actual prevalence among patients with mild TSH elevations (as those found in mild hypothyroidism) is so far unknown. In this study, we eval...