Centralized and standardized molecular testing for genetic alterations associated with a high risk of malignancy efficiently complements the local cytopathologic diagnosis of thyroid nodule aspirates in the clinical setting. Actionable molecular cytology can improve the personalized surgical and medical management of patients with thyroid cancers, facilitating one-stage total thyroidectomy and reducing the number of unnecessary diagnostic surgeries.

We studied various tests of thyroid function in sick patients with nonthyroidal illness (NTI) in order to determine the utility of each test for differentiating these patience from a group with hypothyroidism. We evaluated each test in 22 healthy volunteers who served as controls, 20 patients with hypothyroidism, 14 patients admitted to medical intensive care unit whose serum T4 was less than 5 micrograms/dl, 13 patients with chronic liver disease, 32 patients on chronic hemodialysis for renal failure, 13 ambulatory oncology patients receiving chemotherapy, 16 pregnant women, 7 women on estrogens, and 20 hyperthyroid patients. On all samples, we measured serum T4, the free T4 index by several methods, free T4 by equilibrium dialysis, free T4 calculated from thyronine-binding globulin (TBG) RIA, free T4 by three commercial kits (Gammacoat, Immophase, and Liquisol), T3, rT3, and TSH (by 3 different RIAs). Although all of the methods used for measuring free T4 (including free T4 index, free T4 by dialysis, free T4 assessed by TBG, and free T4 assessed by the 3 commercial kits) were excellent for the diagnosis of hypothyroidism, hyperthyroidism, and euthyroidism in the presence of high TBG, none of these methods showed that free T4 was consistently normal in patients with NTI; with each method, a number of NTI patients had subnormal values. In the NTI groups, free T4 measured by dialysis and the free T4 index generally correlated significantly with the commercial free T4 methods. Serum rT3 was elevated or normal in NTI patients and low in hypothyroid subjects. Serum TSH provided the most reliable differentiation between patients with primary hypothyroidism and those with NTI and low serum T4 levels.

The hyperthyroid state in vivo is associated with an increase in osteoblast number and activity, suggesting that thyroid hormone may stimulate osteoblast replication and function. We therefore examined the effects of T3 (16-1170 pM) on replication rate as assessed by cell counts in UMR-106 osteoblastic osteosarcoma cells cultured for 5-10 days in medium supplemented with 10% hormone-stripped fetal calf serum (FCS). Despite the virtual absence of thyroid hormone in the control medium (total T3 concentration, 0.02 ng/ml), the addition of T3 in concentrations to 1000 pM did not increase the cell replication rate. At higher T3 concentrations, a slight decrease in growth rate was observed. No significant 5'-monodeiodinase activity was detected in UMR-106 cell homogenates. However, nuclear binding of T3 was demonstrated in intact cells. A high-affinity nuclear binding component was identified with a Ka of 2.6 x 10(10) M-1 and a maximum binding capacity of 7.7 pg T3 per mg DNA, equivalent to 51 binding sites per cell nucleus. A lower affinity nuclear T3 binding component with a Ka of 1.8 x 10(9) M-1 was also identified. Thus, despite the presence of nuclear T3 receptors, UMR-106 cells do not exhibit a mitogenic response to T3.

High levels of thyrotropin releasing hormone (TRH) and TRH-homologous peptide, with the general structure pGlu=X-Pro-NH2 where X is either Histidine (His) or a neutral amino acid residue, have been identified in rat and human prostate (Pekary et al, 1980, 1981a, 1982c). Because of the secretory nature of prostatic tissue, it was considered likely that these peptides would be measurable in human semen. The mean (+/- SD) TRH immunoreactivity (TRH IR) in semen from 26 normal donors, aged 26 and 41 years, was found to be 12.2 +/- 5.2 ng/ml. TRH and TRH-homologous peptide, were undetectable in unconcentrated human serum. TRH IR levels in semen from azoospermic donors were in the normal range. The level of TRH IR in semen from vasectomized donors was significantly less (P less 0.01) than in semen from normal subjects. Evidence for at least two TRH-binding substances, which coextract and bind to added synthetic TRH, was obtained by exclusion and cation exchange chromatography. Purification of extracts of human semen by TRH affinity chromatography or gradient, reversed phase high pressure liquid chromatography (HPLC) revealed two major TRH immunoreactive peptides, one corresponding to the TRH-homologous peptide previously reported in rat and human prostate and one cochromatographing with synthetic TRH.