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Endocrine and liver interaction: the role of endocrine pathways in NASH

Nature Reviews Gastroenterology & Hepatology volume 6, pages 236–247 (2009)Cite this article

Abstract

This article reviews evidence that causally links hormonal disorders with hepatobiliary disease, and gives particular focus to nonalcoholic steatohepatitis (NASH). The downstream mechanisms by which endocrine disturbances cause liver disease might be similar to those involved in the development of primary liver disease. Hypothyroidism, for example, might lead to NASH, cirrhosis and potentially liver cancer via the development of hyperlipidemia and obesity. Patients with growth hormone deficiency have a metabolic-syndrome-like phenotype that is also associated with the development of NASH. Polycystic ovary syndrome is a common endocrine disorder that is often associated with insulin resistance, the metabolic syndrome, altered levels of liver enzymes and the development of NASH. Recent findings support a role of dehydroepiandrosterone sulfate deficiency in the development of advanced NASH. In addition, adrenal failure is increasingly reported in patients with end stage liver disease and in patients who have received a liver transplant, which suggests a bidirectional relationship between liver and endocrine functions. Clinicians should, therefore, be aware of the potential role of endocrine disorders in patients with cryptogenic liver disease and of the effects of liver function on the endocrine system.

Key Points

  • A proportion of patients who have cryptogenic cirrhosis without identifiable etiology of liver disease are expected to have cirrhosis as a complication of nonalcoholic steatohepatitis (NASH)

  • Endocrine hormones control cell metabolism and the distribution of body fat; therefore, endocrine dysfunction might lead to metabolic liver disease in some patients who will eventually be diagnosed with cryptogenic cirrhosis

  • Hypothyroidism is associated with NASH, hepatocellular carcinoma and biliary stones, and dehydroepiandrosterone sulfate (DHEA-S) might have a role in fibrosing NASH

  • Growth hormone deficiency can cause a metabolic-syndrome-like phenotype, the metabolic derangements of which might induce the development of NASH

  • Polycystic ovary syndrome is associated with the development of nonalcoholic liver disease

  • Specific endocrine disorders might promote metabolic liver disease and, given that treatment is available for such endocrine disorders, endocrine etiologies should be ruled out in patients with cryptogenic cirrhosis

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Figure 1: Influence of hypothyroidism on hepatobiliary function.
Figure 2: Cholesterol and bile acid metabolism in hyperthyroid and hypothyroid patients.
Figure 3: Liver disease, including nonalcoholic steatohepatitis, might arise secondary to the metabolic effects of endocrine disturbances: hypothyroidism, GH deficiency, DHEAS deficiency and PCOS.

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  1. Dipartimento di Endocrinologia, Metabolismo e Geriatria, Università degli Studi di Modena e Reggio Emilia, NOCSAE–Baggiovara, Modena, MO, Italy

    Paola Loria, Lucia Carulli, Marco Bertolotti & Amedeo Lonardo

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  2. Lucia Carulli
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  3. Marco Bertolotti
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  4. Amedeo Lonardo
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Correspondence to Paola Loria.

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Loria, P., Carulli, L., Bertolotti, M. et al. Endocrine and liver interaction: the role of endocrine pathways in NASH. Nat Rev Gastroenterol Hepatol 6, 236–247 (2009). https://doi.org/10.1038/nrgastro.2009.33

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