The Influences of TSH Stimulation Level, Stimulated Tg Level and Tg/TSH Ratio on the Therapeutic Effect of 131I Treatment in DTC Patients

PurposeTo study the influences of pre-ablation TSH stimulation level, sTg and sTg/TSH ratio on the therapeutic effect of the first 131I treatment in DTCs.MethodsAccording to the thyroid stimulating hormone (TSH) levels (mU/l), all the 479 differentiated thyroid cancer (DTC) patients were divided into two groups: TSH < 30 and TSH ≥ 30. The TSH ≥ 30 group was divided into three subgroups: 30 ≤ TSH < 60, 60 ≤ TSH < 90 and TSH ≥ 90. The clinical features and the therapeutic effects of the first 131I treatment were analyzed. The cutoffs of stimulated thyroglobulin (sTg) and sTg/TSH ratio were calculated to predict the therapeutic effect of 131I treatment.ResultsAmong the three subgroups, the TSH ≥ 90 subgroup was younger and less likely to be associated with cervical lymph node metastasis (LNM). The postoperative levothyroxine (L-T4) dose in the 60 ≤ TSH < 90 subgroup was the lowest. Between the two groups, patients in the TSH < 30 group had higher postoperative L-T4 dose and longer thyroid hormone withdrawal (THW) time. The excellent response rates six months after the first 131I treatment among the three subgroups and between the two groups were not of statistical significance. The distribution of different TSH stimulation levels among each response group was similar. The cutoffs for the better therapeutic effect of the first 131I treatment in sTg and sTg/TSH were < 9.51 ng/ml and < 0.11, respectively. Both univariate and multivariate logistic regressions showed that cervical LNM, distant metastasis, higher sTg and higher sTg/TSH ratio predicted poorer therapeutic effect.ConclusionsThere was no significant influence of TSH stimulation levels before the first 131I treatment on the therapeutic effect of DTC. The sTg/TSH ratio can be considered as another predictor of 131I therapeutic effect.

The tissue-specific pathways regulating cell proliferation are inherited independently in somatic hybrid between thyroid and liver cells.

Thyroid stimulating hormone (TSH) and insulin-like growth factors type 1 (IGF-I) regulate the proliferation and differentiation of cultured thyroid cells but not of cultured liver cells. We have examined the influence of TSH and IGF-I on the metabolic functions and proliferation of somatic hybrids obtained by fusing rat thyroid cells (FRTL5) with rat liver cells (BRL). While IGF-I is able to stimulate the proliferation of the hybrid cells (TxL) TSH fails to induce their growth. However, the hybrid TxL cells have surface TSH receptors with normal ligand characteristics. The addition of TSH to TxL cells led to typical enhancement of cAMP production and depolymerization of actin filaments. Yet, TSH failed to stimulate iodine uptake in the hybrid cells. Interestingly, iodine inhibited TxL proliferation induced by IGF-I but not by serum. It is concluded that the hybrid TxL cells inherited from the parental thyroid cells several important differentiated traits including mitogenic pathways induced and used by IGF-I, functional TSH receptors, and sensitivity to the inhibitory action of iodine.

The influence of TSH and ACTH on purine and pteridine deposition in the skin of rainbow trout (Salmo gairdneri)

The specific activities (s.a.) and levels of skin purines and pteridines were determined in 1-year-old rainbow trout that were injected with [14C]glycine and treated for 20–28 days with bovine thyroid-stimulating hormone (TSH) or adrenocorticotropic hormone (ACTH). TSH increased significantly the s.a. and levels of guanine and hypoxanthine, but had no effect on these parameters for guanosine monophosphate (GMP), biopterin, 2-amino-4-hydroxypteridine (AHP), and ichthyopterin. The s.a. of isoxanthopterin (IXP) was significantly decreased. ACTH increased significantly the s.a. and levels of GMP, biopterin, AHP, IXP, and ichthyopterin. The s.a. and levels of guanine and hypoxanthine were not altered significantly. Thus TSH promotes purine synthesis with no significant change in the synthesis of most pteridines, while ACTH promotes pteridine synthesis with no significant change in purine synthesis. These observations on trout skin do not favour a previously advanced generalization that purine and pteridine biosynthetic pathways compete for a common substrate.

THE INHIBITION OF [35S]THIOCYANATE METABOLISM IN THE THYROID GLAND BY THYROID-STIMULATING HORMONE

SUMMARY When potassium [35S]thiocyanate was administered to rats, treatment with thyroid-stimulating hormone (TSH) diminished the amount of 35S per unit weight of thyroid, as well as the thyroid:plasma 35S ratio (T:P) for compounds containing 35S. Chromatographic analysis of thyroid gland homogenates and plasma showed that under the influence of TSH the 35SCN-fraction increased, while the 35SO42− fraction decreased in the thyroid. The T:P ratio calculated for both fractions confirmed the increase of the 35SCN-concentration in the thyroid. Chromatographic analysis of the plasma showed that the 35SCN− fraction in the TSH-treated animals increased gradually while it decreased in the control group. Experiments with guinea-pig thyroid lobes in vitro agreed with the results in vivo. A significant increase of 35SCN− and a decrease in 35SO42− were found in TSH-treated thyroids after 6 h of incubation. Even clearer results were obtained by analysis of the medium. Oxidation of [35S]thiocyanate to [35S]sulphate, with a simultaneous release into the medium of the latter, took place only in the control thyroid lobes. In the TSH-treated thyroids, no changes were found in the percentage content of 35S compounds in the medium during 6 h of incubation. These results suggest that TSH inhibits the degradation of thiocyanate in the thyroid.

A CORRELATIVE STUDY OF ULTRASTRUCTURE AND FUNCTION OF THE THYROID GLAND OF THE GOLDEN HAMSTER

ABSTRACT Three procedures were used to stimulate thyroid function in the golden hamster 1) administration of thyrotrophin (TSH), 2) propylthiouracil (PTU) feeding; and 3) cold exposure. In the three experimental conditions, the composite of functional and morphological responses of the thyroid gland differed. Thyroid glands of TSH and PTU-treated hamsters, but not cold-exposed animals were characterized by marked increase in weight, due predominantly to increase in mass of epithelial cells; follicular epithelial cells of TSH and PTU-treated glands exhibited striking expansion and dilatation of the endoplasmic reticulum and enlargement of the Golgi apparatus. These structural changes were not necessarily concomitants of increased thyroid hormone synthesis, since they were exhibited by glands from PTU-treated animals. Glands of TSH and PTU-treated animals also displayed marked increases in the number of microvilli and apical vesicles. Comparable increases were not seen in cold-exposed animals, even though some functional criteria of activity suggested that these glands were under the influence of TSH. The significance of this is discussed.

A COMPARISON OF THE IN-VITRO ACTIONS OF THYROID-STIMULATING HORMONE AND CYCLIC 3′,5′-ADENOSINE MONOPHOSPHATE ON THE MOUSE THYROID GLAND

SUMMARY In the in-vitro assay of Brown & Munro (1967) thyroid-stimulating hormone (TSH) increased the release of radioactive iodine from mouse thyroid glands labelled with 131i during life. Paper chromatography showed that TSH increased the 131I-labelling of thyroxine and tri-iodothyronine both in the culture medium and in hydrolysates of the thyroids. Cyclic 3′,5′-adenosine monophosphate (cyclic AMP) also increased 131I release in this assay and increased the 131I-labelling of thyronines in the culture medium. The effects on thyroid hydrolysates were less striking. Theophylline potentiated the influence of TSH and cyclic AMP in the assay and, by itself, increased 131I release and the labelling of iodothyronines in the thyroid without altering the distribution of 131I in the culture medium. The implications of these results are discussed.