Hypothyroidism and Nonalcoholic Fatty Liver Disease: Pathophysiological Associations and Therapeutic Implications

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a complex clinical entity which can be secondary to many other diseases including hypothyroidism, characterized by lowering of thyroid hormones and increased thyroid stimulating hormone (TSH). A lot of emerging data published recently advocates the hypothesis that hypothyroid induced NAFLD could be a separate clinical entity, even suggesting possible treatment options for NAFLD involving substitution therapy for hypothyroidism along with lifestyle modifications. In addition, a whole new field of research is focused on thyromimetics in NAFLD/NASH treatment, currently in phase 3 clinical trials. In this critical review we summarized epidemiological and pathophysiological evidence linking these two clinical entities and described specific treatment options with the accent on promising new agents in NAFLD treatment, specifically thyroid hormone receptor (THR) agonist and its metabolites.

Obesity and Thyroid Axis

“…In our previous study [104], the metabolic syndrome was connected with visceral fat accumulation and higher TSH concentrations. Obesity and metabolic syndrome are strongly associated with NAFLD which is characterized by enhanced hepatic lipogenesis, and it is believed that increased TSH accelerates the development of NAFLD and nonalcoholic steatohepatitis (NASH) [115]. It was documented that downregulation of the leptin pathway and decreased expression of DIO2, DIO3 and genes regulated by THs in the liver may cause fat accumulation that leads to NAFLD [80].…”

Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD

“…The pathophysiological hypothesis underlying this epidemiological association seems to be the development of insulin resistance in hypothyroidism, probably through increased oxidative stress, lipid peroxidation and the rise of several adipocytokines such as leptin and tumor necrosis factor α (TNFα) [ 78 ]. Some advocate that hypothyroidism-induced NAFLD could be a separate clinical entity with specific treatment options [ 79 ].…”

La Non-Alcoholic Fatty Liver Disease, una patologia epatica di interesse endocrinologico

“…D’altro canto, dati pubblicati di recente sostengono l’ipotesi che la NAFLD indotta dall’ipotiroidismo possa essere considerata un’entità clinica separata, suggerendo anche possibili opzioni di trattamento per la NAFLD attraverso la terapia sostitutiva per l’ipotiroidismo insieme a modifiche dello stile di vita. Inoltre, un intero nuovo campo di ricerca è focalizzato sui tiromimetici nel trattamento NAFLD/NASH, attualmente in fase 3 di sperimentazione clinica [ 25 ].…”