Immunohistochemistry in detection of paraneoplastic secretion of calcium regulating hormones

29 non-endocrine tumors with clinical suspicion of paraneoplastic hypercalcemia were examined using immunohistochemistry specific for PTH and CT. In 19 of these cases intracellular immunoprecipitates have been demonstrable thus showing the paraneoplastic production of peptide hormones (18 PTH, 1 CT). Four of these tumors have been tested in tissue culture for in vitro production of endocrine active substances. In all cases the incubation medium yielded a positive reaction for PTH. The use of immunocytochemistry in the differential diagnosis of hypercalcemia in tumor patients is discussed.     

Neuroendocrine interactions in thyroid pathology

Neuroendocrine interactions in thyroid pathology were studied by means of recording and analysis of the constant potential level (CPL) of the brain. The topography of changes in cerebral metabolism upon changes in the thyroid status was determined. A twofold CPL decrease in the central and left temporal areas was shown in hypothyroidism as compared with euthyroidism; in hyperthyroidism, there was a threefold CPL increase in the occipital area and a twofold CPL increase in the frontal and temporal areas as compared to euthyroidism. These variations were associated with corresponding changes in the metabolism of the brain’s energy. The constant potential value averaged over all derivations was approximated by the linear dependence on the logarithms of concentrations of the thyrotropic hormone (TTH), r = ?0.70, (p < 0, 001), n = 82. Drawing the dependences of the CPL value in derivation sites on the TTH concentration on a semilogarithmic scale, yielded approximation equations with negative correlation coefficients of ?0.53 to ?0.7. The method allows for the monitoring of the state of patients and assessment of the efficiency of treatment for thyroid pathology by the change in the CPL in different regions of the brain.     

Proteome analysis in thyroid pathology

The incidence of thyroid cancer has continuously increased due to its detection in the preclinical stage. Clinical research in thyroid pathology is focusing on the development of new diagnostic tools to improve the stratification of nodules that have biological, practical and economic consequences on the management of patients. Several clinical questions related to thyroid carcinoma remain open and the use of proteomic research in the hunt for new targets with potential diagnostic applications has an important role in the solutions. Many different proteomic approaches are used to investigate thyroid lesions, including mass spectrometry profiling and imaging technologies. These approaches have been applied to different human tissues (cytological specimens, frozen sections, formalin-fixed paraffin embedded tissue or Tissue Micro Arrays). Moreover, other specimens are used for biomarker discovery, such as cell lines and the secretome. Alternative approaches, such as metabolomics and lipidomics, are also used and integrated within proteomics.     

Metabolism of the thyroid hormones

This review covers the current knowledge about the various metabolic pathways involved in the conversion of thyroid hormones to the thyromimetically active and inactive iodothyronines. The concerted mechanism of systemic and local production of iodothyronines by tissue-specific iodothyronine deiodinase isozymes will ultimately determine the expression of thyroid hormone action. This is exemplified for the regulation of synthesis and release of TSH by iodothyronines at the pituitary level. Iodothyronine metabolites, e.g. Triac, rT3 and T3 amine may modulate TSH secretion, and alterations of local pituitary deiodination (e.g. iopanoate inhibition) influence diurnal TSH secretion without changing TRH-dependent episodic TSH secretion pattern. A summary of structure-activity relationships of greater than 200 naturally occurring and synthetic ligands of rat liver type I iodothyronine deiodinase isozyme propylthiouracil-sensitive) in vitro allows the design of iodothyronine analogues which either serve as specific substrates or antagonists of iodothyronine binding and metabolizing proteins. Furthermore, a complete picture of the ligand-complementary active site of the type I isozyme can be derived. A synthetic 'structurally optimized' iodothyronine-analogue flavonoid inhibitor of the type I deiodinase is able to displace T4 from binding to thyroxine-binding prealbumin and leads to unexpected organ-specific alterations of thyroid hormone metabolism and expression of thyroid hormone actions in an animal model. Therefore, for a complete understanding of thyroid hormone metabolism and action, thyroid hormone transport, cellular compartmentalization, and alternate pathways also have to be considered.     

Membrane reception of thyroid hormones]

Comparative and competitive analyses of thyroxine (T4) and triiodothyronine (T3) binding to highly purified rat liver, brain and lung cell plasma membranes were carried out. The dependence of hormone binding on the time, temperature and concentration was studied. The effects of trypsin and partial delipidation on the binding parameters of thyroid hormones were investigated. Two thyroid hormone-binding sites were detected in cell plasma membranes of all tissues under study. The maximal binding of T4 to rat liver membranes and the maximal binding of T3 to rat brain membranes was observed in all experiments, the affinity for T3 being higher than that for T4. An important role of both protein and lipid components of plasma membranes in the membrane reception of thyroid hormones is proposed.