Dataset Information

Hypothyroidism symptoms in LT4-euthyroid thyroidectomized patients reflect an alteration of the serum proteome

ABSTRACT: In patients undergoing thyroidectomy one of the goals of post-surgical follow-up is the correct maintenance of thyroid hormone (TH) levels by replacement therapy with levo-thyroxine (LT4). Nevertheless, some patients complain of symptoms of hypothyroidism (memory loss, weight gain, fatigue, depression, and reduced quality of life) despite values of thyroid hormones get the physiological range. Since this recurrent issue, we aim to compare serum proteomic profiles of LT4-euthyroid thyroidectomized patients with stable or reduced post-operative quality of life. Proteomic analysis highlights a different protein profile in serum of patients with reduced quality of life compared to the other although both resulted euthyroid. Differential proteins are involved in coagulation processes, complement system activation and in lipoprotein particles remodeling, that together lead to a pro-inflammatory response. Moreover, a particular protein isoform pattern of apolipoprotein A1 and alpha 1 antitrypsin, was also detected. This study suggests that LT4 replacement therapy might restore euthyroid conditions in thyroidectomized patients but in some cases without re-establish body tissues euthyroidism. This condition is reflected by the serum protein profile that shows a behavior similar to overt hypothyroidism.

INSTRUMENT(S): ultraflex

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Serum

SUBMITTER: Enxhi Shaba

LAB HEAD: Luca Bini

PROVIDER: PXD028378 | Pride | 2022-04-04

REPOSITORIES: Pride

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Alteration of Serum Proteome in Levo-Thyroxine-Euthyroid Thyroidectomized Patients.

Landi Claudia C Cantara Silvia S Shaba Enxhi E Vantaggiato Lorenza L Marzocchi Carlotta C Maino Fabio F Bombardieri Alessio A Carleo Alfonso A Di Giuseppe Fabrizio F Angelucci Stefania S Bini Luca L Castagna Maria Grazia MG

Journal of clinical medicine 20220317 6

The monotherapy with levo-thyroxine (LT4) is the treatment of choice for patients with hypothyroidism after thyroidectomy. However, many athyreotic LT4-treated patients with thyroid hormones in the physiological range experience hypothyroid-like symptoms, showing post-operative, statistically significant lower FT3 levels with respect to that before total thyroidectomy. Since we hypothesized that the lower plasmatic FT3 levels observed in this subgroup could be associated with tissue hypothyroidi ...[more]

PMID: 35330001

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Project description:Transcriptional profiling of rat liver comparing male rats with congenital hypothyrodism (CH) vs intact at adulhood. Here we studied how CH influences liver gene expression program in adulthood. Thyroid hormones are required for normal growth and development in mammals. Congenital-neonatal hypothyroidism (CH) has a profound impact on physiology but its specific influence in liver is less understood. Here we studied how CH influences liver gene expression program in adulthood. Pregnant rats were given anti-thyroid drug methimazole (MMI) from GD12 until PND30 to induce CH in male offspring. Growth defects due to CH were evident as a reduction in body weight and tail length from the second week of life. Once the MMI treatment was discontinued, feed efficiency increased in CH and this was accompanied by significant catch-up growth. On PND80, significant reduction in body mass, tail length, and circulating IGF-I remained in CH rats. On the other hand, mRNA levels of known GH targeted genes were significantly up-regulated. Serum levels of thyroid hormones, cholesterol, and triglycerides showed no significant differences. In contrast, CH rats showed significant changes in expression for hepatic genes involved in lipid metabolism with an increased transcription of PPAR and reduced expression of genes involved in fatty acids and cholesterol uptake, cellular sterol efflux, triglycerides assembly, bile acid synthesis, and lipogenesis. These changes were associated with a decrease of intrahepatic lipids. Finally, CH rats responded to hypothyroidism onset in adulthood with a reduction of serum fatty acids and hepatic cholesteryl esters, and to T3 replacement with enhanced activation of lipogenic transcriptional program. In summary, we provided in vivo evidence that neonatal hypothyroidism causes long-lasting effects on hepatic transcriptional program and tissue sensitivity to hormone treatment. This highlights the critical role that a euthyroid state during development plays on normal liver physiology in adulthood. Two conditions CH vs INTACT male rats. Biological replicates: Four independent hybridizations: 4 controls (age-matched intact rats) vs 4 CH (male rats with congenital hypothyroidism) on postnatal day 80 for a total of four arrays. One replicate per array.

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