Low-dose radioiodine therapy for patients with intermediate- to high-risk differentiated thyroid cancer.

OBJECTIVE: The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the country's shortage of medical facilities for RIT, 1110-MBq RIT for higher risk DTC patients has been performed on an outpatient basis since 2010 in Japan. Herein, we addressed this issue and attempted to determine prognostic factors for the prediction of RIT outcomes. METHODS: We retrospectively analyzed the cases of 119 patients with papillary thyroid cancer who underwent their first RIT with 1110 MBq radioactive iodine (RAI) following a total thyroidectomy, including 65 (54.6%) intermediate-risk and 54 (45.4%) high-risk patients (according to Japan's 2018 clinical practical guidelines for thyroid tumors). Successful ablation was defined when a negative I-131 whole-body scan and thyroglobulin (Tg) < 2 ng/mL were obtained at a diagnostic scan performed 148-560 days (median 261 days) after the first RIT. RESULTS: The overall ablation success rate was 23.4%. Although the ablation success rates of each pretreatment protocol [recombinant human thyroid stimulating hormone and thyroid hormone withdrawal (THW)] did not differ significantly, THW tended to result in a higher success rate than rhTSH. The Tg level at RIT was the only independent powerful predictive factor for successful ablation. The best cut-off value of Tg for predicting unsuccessful ablation was 9 ng/mL. CONCLUSIONS: The ablation success rate was much lower than those of earlier studies; the most plausible reason would be that higher risk DTC patients were included in this study. The low-dose RIT routinely performed in Japan might be inadequate for the achievement of successful ablation. At least for patients with Tg > 9 ng/mL at the first RIT, a higher dose of RAI is recommended.

Adipose tissue TSH as a new modulator of human adipocyte mitochondrial function.

BACKGROUND/OBJECTIVES: Recent studies indicate a possible role of TSH/TSHR signalling axis on adipogenesis and adipose tissue physiology. Here, we aimed to investigate the relationship between adipose tissue TSHB and adipose tissue physiology-related gene expression. SUBJECTS/METHODS: Subcutaneous and visceral adipose tissue TSHB gene expression was analysed in two independent cohorts [Cohort1 (N = 96) and Cohort2 (N = 45)] and after bariatric surgery-induced weight loss [Cohort3 (N = 22)]. Adipose tissue TSH protein expression was also analysed in a subgroup of participants from Cohort 1 (N = 16). The effects of recombinant TSH on human subcutaneous preadipocytes and adipocytes were investigated. RESULTS: In cohort 1, both visceral and subcutaneous adipose tissue TSHB gene expression was positively correlated with the expression of mitochondrial function (PPARGC1A, ISCA2, CISD1, SIRT1, NFE2L2, NRF1) and fatty acid mobilization (CAV1, ENGL1), but not with adipogenic-related genes. Of note, adipose tissue TSH protein levels were also associated with some of these markers of mitochondrial function and fatty acid mobilization. These associations were replicated in cohort 2. Bariatric surgery-induced weight loss resulted in increased subcutaneous adipose tissue TSHB in parallel to increased PPARGC1A. In human subcutaneous adipocytes, rh-TSH administration led to increased mitochondrial respiratory capacity in parallel to increased mitochondrial function- and adipogenic-related gene expression, but no significant effects were observed during differentiation of human preadipocytes. CONCLUSION: These data point to a possible role of adipose tissue TSH in the maintenance of adipocyte mitochondrial function.

TSH-induced gene expression involves regulation of self-renewal and differentiation-related genes in human bone marrow-derived mesenchymal stem cells.

Bone marrow-derived mesenchymal stem cells are pluripotent cells that are capable of differentiating into a variety of cell types including neuronal cells, osteoblasts, chondrocytes, myocytes, and adipocytes. Despite recent advances in stem cell biology, neuroendocrine relations, particularly TSH interactions remain elusive. In this study, we investigated expression and biological consequence of TSH receptor (TSHR) interactions in mesenchymal stem cells of cultured human bone marrow. To the best of our knowledge, we demonstrated for the first time that human bone marrow-derived mesenchymal stem cells expressed a functional thyrotropin receptor that was capable of transducing signals through cAMP. We extended this study to explore possible pathways that could be associated directly or indirectly with the TSHR function in mesenchymal stem cells. Expression of 80 genes was studied by real-time PCR array profiles. Our investigation indicated involvements of interactions between TSH and its receptor in novel regulatory pathways, which could be the important mediators of self-renewal, maintenance, development, and differentiation in bone marrow-derived mesenchymal stem cells. TSH enhanced differentiation to the chondrogenic cell lineage; however, further work is required to determine whether osteoblastic differentiation is also promoted. Our results presented in this study have opened an era of regulatory events associated with novel neuroendocrine interactions of hypothalamic-pituitary axis in mesenchymal stem cell biology and differentiation.

Acute effect of TSH on oxygenation state and volume of erythrocytes from subjects thyroidectomized for differentiated thyroid carcinoma.

We previously reported the presence in the membrane erythrocyte of a TSH receptor (TSHR), a G-protein coupled receptor, which responds to TSH with increased cAMP level. Since there is evidence for a role of G protein receptors as oxygen sensor(s) implicated in cell volume regulation, we hypothesized that erythrocyte TSHR, by TSH stimulation, could modify the erythrocyte volume and the oxygenation state of erythrocytes. We determined the effect of TSH on the gas analysis in 35 thyroidectomized patients for stage I differentiated thyroid cancer enrolled for recombinant human thyroid-stimulating hormone (rhTSH) test during chronic treatment with synthetic l-thyroxine. Moreover, we explored the influence of TSH on the shape of erythrocytes. Venous blood-gas analysis before and after TSH were determined with a pH/blood gas electrolyte and 682 CO-Oxymeter. In a subgroup of subjects (n=10), the isolated red blood cells (RBC) were analyzed by flow cytometry for morphological changes. After TSH stimulation, we found a significant decrease in PCO(2) (P<0.001), an increase in pH (P<0.01) and an increase of % O(2)-Hb (P<0.05) and pO(2) (P<0.05). By flow cytometry, the erythrocytes after TSH showed a significant enrichment on the mean number in the selected region R1 corresponding to bigger volumes (P<0.05, n=10). Finally, by contrast phase microscopy, when the cell area was measured, a mean increased volume was observed in erythrocytes after TSH compared to the basal before TSH (P<0.05). In conclusion, our results indicate that acute stimulation of TSH by rhTSH modifies the oxygenation state and volume of erythrocyte.

[Manifestations and prognosis of thyrotropin-secreting pituitary adenomas: a case series of three patients]. / Présentation et pronostic des adénomes thyréotropes: à propos de trois observations.

INTRODUCTION: Among pituitary adenomas, thyrotropinomas were previously considered as extremely rare and resistant to therapy. However, the common use of the sensitive TSH measurement and the improvement of pituitary imaging have modified their clinical and hormonal presentation. CASE REPORTS: We here report three cases of TSH secreting pituitary adenoma that highlight the great diversity of the clinical, hormonal and morphological presentation, and their better prognosis. In the presence of an inappropriate TSH secretion, the main differential diagnosis is the syndrome of thyroid hormone resistance. The role of somatostatin analogue prior to the surgical treatment of TSH secreting pituitary adenoma is also underlined in this report. CONCLUSION: The increasing frequency and early diagnosis of TSH secreting pituitary adenoma may be explained by ultrasensitive methods now used for TSH measurement and progress in pituitary imaging, mainly with MRI. This changing spectrum in the presentation and the excellent response to somatostatin analogues improved in the prognosis of the disease.