Effects of Thyrotropin on Peripheral Thyroid Hormone Metabolism and Serum Lipids

Beukhof, Carolien; Massolt, Elske T.; Visser, Theo J.; Korevaar, Tim I M; Medici, Marco; Herder, Wouter W. de; Lennep, Jeanine E. Roeters van; Mulder, Monique; Rijke, Yolanda B. de; Reiners, Christoph; Verburg, Frederik A.; Peeters, Robin P.

doi:10.1089/thy.2017.0330

Cited by 28 publications

(20 citation statements)

References 45 publications

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“…A recent study reported the effect of rhTSH on 82 patients with differentiated thyroid cancer, previously treated with total thyroidectomy and 131 I remnant ablation [26]. The analyses showed a decrease of HDL, from 0.92 to 0.81 mmol/L (p < 0.001), and increase of triglycerides from 1.98 to 2.50 mmol/L (p < 0.001), both associated with the decrease of T3 level.…”

Section: Discussionmentioning

confidence: 97%

Effect of rhTSH on Lipids

Delitala

Scuteri

Maioli

et al. 2020

JCM

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Background: Subclinical hypothyroidism is associated with increased blood lipid levels. However, the exact role of thyrotropin (TSH) alone is not clear. In order to clarify this point, we analysed the acute effect of recombinant human TSH (rhTSH) administration on lipid levels. Methods: Sera of 27 premenopausal women with well-differentiated thyroid cancer were analysed. Patients that underwent a total thyroidectomy, ablation with 131I (Iodine 131) and rhTSH administration as a part of routine follow-up American Thyroid Association guidelines were included. The protocol consists of 2 intramuscular injections of 0.9 mg of rhTSH, performed on day 1 day and day 2, with blood collection on day 1 (before rhTSH administration), and day 5. TSH, free thyroxine, total cholesterol, low-density lipoprotein cholesterol (LDLc), high density lipoprotein cholesterol (HDLc), and triglycerides were assessed in all the samples, before and four days after the first administration of rhTSH. Results: Total cholesterol and triglycerides significantly increased after stimulation of rhTSH (respectively, 192 ± 33 vs. 207 ± 26, p = 0.036 and 72 ± 23 vs. 85 ± 23, p = 0.016). LDLc and HDLc showed comparable concentrations before and after the test (respectively, 115 ± 27 vs. 126 ± 22, p = 0.066, and 62 ± 15 vs. 64 ± 15, p = 0.339), while non-HDLc increased after stimulation (130 ± 30 vs. 143 ± 25, p = 0.045). Conclusion: TSH has a direct effect on total cholesterol, triglycerides, and nonHDLc. Explanation of these phenomena will require additional studies.

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Section: Discussionmentioning

confidence: 97%

Effect of rhTSH on Lipids

Delitala

Scuteri

Maioli

et al. 2020

JCM

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“…In this context, TSH directly increased lipogenesis by activating SREBP1c via a cAMP/PKA/PPARα signaling pathway associated with AMPK in hepatic cells (101). Recently, it was shown that the administration of recombinant human TSH increases serum apoB, Lp(a), non-HDL cholesterol, and TAGs in patients after thyroidectomy on a stable dose of LT4 (102). After TSH administration, T3 levels were reduced and changes in lipids were inversely associated with the T3 levels, suggesting that TSH may have had an indirect effect on lipid levels (102), perhaps due to effects on the deiodinase activity.…”

Section: Tsh and Lipid Metabolismmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists

Sinha

Bruinstroop

Singh

et al. 2019

Thyroid

178

131

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Background-Thyroid hormones (THs) exert a strong influence on mammalian lipid metabolism at the systemic and hepatic levels by virtue of their roles in regulating circulating lipoprotein, triglyceride (TAG), and cholesterol levels, as well as hepatic TAG storage and metabolism. These effects are mediated by intricate sensing and feedback systems that function at the physiological, metabolic, molecular, and transcriptional levels in the liver. Dysfunction in the pathways involved in lipid metabolism disrupts hepatic lipid homeostasis and contributes to the pathogenesis of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and hypercholesterolemia. There has been strong interest in understanding and employing THs, TH metabolites, and TH mimetics as lipid-modifying drugs. Summary-THs regulate many processes involved in hepatic TAG and cholesterol metabolism to decrease serum cholesterol and intrahepatic lipid content. TH receptor β analogs designed to have less side effects than the natural hormone are currently being tested in phase II clinical studies for NAFLD and hypercholesterolemia. The TH metabolites, 3,5-diiodo-L-thyronine (T2) and T1AM (3-iodothyronamine), have different beneficial effects on lipid metabolism compared with triiodothyronine (T3), although their clinical application is still under investigation. Also, prodrugs and glucagon/T3 conjugates have been developed that direct TH to the liver. Conclusions-TH-based therapies show clinical promise for the treatment of NAFLD and hypercholesterolemia. Strategies for limiting side effects of TH are being developed and may enable TH metabolites and analogs to have specific effects in the liver for treatments of these conditions. These liver-specific effects and potential suppression of the hypothalamic/pituitary/

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“…Of note, given that progression of the disease is accompanied by significantly decreased nitrite and nitrate levels, nitric oxide (NO) levels could be a reliable biomarker for cardiovascular risk in SCH ( 77 ). Recently, a retrospective analysis of 82 thyroidectomized patients with differentiated thyroid cancer showed that following stimulation by recombinant human TSH (rhTSH), serum T3 concentrations decreased (from 1.91 to 1.81 nmol/L; p < 0.001), while T4, fT4, and rT3 remained unchanged ( 78 ). Thus, these results may suggest that TSH has a direct effect on peripheral TH metabolism by decreasing T3 in patients receiving L-T4 and that the decline in T3 may cause the dyslipidemic profile.…”

Section: Treatment With L-t4: Why Who and Howmentioning

confidence: 99%

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

2018

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Thyroid dysfunction, manifesting as either overt or subclinical hypothyroidism, negatively affects lipid metabolism: this leads to hypercholesterolemia which progressively increases the risk for cardiovascular disease and, potentially, mortality. Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity. Recently, 3,5-diiodothyronine (T2), a natural thyroid hormone derivative, was found to repress the transcription factor carbohydrate-response element-binding protein (ChREBP) and also to be involved in lipid catabolism and lipogenesis, though via a different pathway than that of T3. While thyroid hormone could therapeutically reverse the dyslipidemic profile commonly occurring in hypothyroidism, it should be borne in mind that the potency of the effects may be age-and sex-dependent. Thyroid hormone administration possibly also sustains and enhances the efficacy of hypolipidemic drugs, such as statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9), in patients with dyslipidemia and hypothyroidism.

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Effects of Thyrotropin on Peripheral Thyroid Hormone Metabolism and Serum Lipids

Abstract: TSH has direct effects on peripheral TH metabolism by decreasing T3 levels in levothyroxine-treated thyroidectomized patients. This decrease in T3 levels is accompanied by unfavorable changes in serum lipids.

Cited by 28 publications

References 45 publications

Effect of rhTSH on Lipids

Effect of rhTSH on Lipids

Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists

A Renewed Focus on the Association Between Thyroid Hormones and Lipid Metabolism

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