The interplay between thyroid and liver: implications for clinical practice.

A complex relationship exists between thyroid and liver in health and disease. Liver plays an essential physiological role in thyroid hormone activation and inactivation, transport, and metabolism. Conversely, thyroid hormones affect activities of hepatocytes and hepatic metabolism. Serum liver enzyme abnormalities observed in hypothyroidism may be related to impaired lipid metabolism, hepatic steatosis or hypothyroidism-induced myopathy. Severe hypothyroidism may have biochemical and clinical features, such as hyperammonemia and ascites, mimicking those of liver failure. Liver function tests are frequently abnormal also in hyperthyroidism, due to oxidative stress, cholestasis, or enhanced osteoblastic activity. Antithyroid drug-associated hepatotoxicity is a rare event, likely related mainly to an idiosyncratic mechanism, ranging from a mild hepatocellular damage to liver failure. Propylthiouracil-induced liver damage is usually more severe than that caused by methimazole. On the other hand, thyroid abnormalities can be found in liver diseases, such as chronic hepatitis C, liver cirrhosis, hepatocellular carcinoma, and cholangiocarcinoma. In particular, autoimmune thyroid diseases are frequently found in patients with hepatitis C virus infection. These patients, especially if thyroid autoimmunity preexists, are at risk of hypothyroidism or, less frequently, thyrotoxicosis, during and after treatment with interpheron-alpha alone or in combination with ribavirin, commonly used before the introduction of new antiviral drugs. The present review summarizes both liver abnormalities related to thyroid disorders and their treatment, and thyroid abnormalities related to liver diseases and their treatment.

Features and outcome of differentiated thyroid carcinoma associated with Graves' disease: results of a large, retrospective, multicenter study.

BACKGROUND: Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves' disease (GD) is more aggressive and bound to a less favorable outcome is controversial. OBJECTIVE: Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD-). PATIENTS: Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD-. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. RESULTS: Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD- patients were free of disease. Patients with persistent or recurrent disease (PRD) had "biochemical disease" in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves' orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism. CONCLUSIONS: GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD.