Clinical spectrum and therapeutic approach to hepatocellular injury in patients with hyperthyroidism

Abstract

Liver dysfunction in patients with hyperthyroidism includes abnormalities associated with the effects of thyroid hormone excess, those secondary to drug-induced liver injury, and changes resulting from concomitant liver disease. Our goal was to describe clinical, biochemical, and histopathological patterns in patients suffering from hyperthyroidism and concomitant liver dysfunction and to propose an algorithm of procedures to facilitate diagnosis and management of such cases. This study describes seven patients with liver biochemistry abnormalities detected after diagnosis of hyperthyroidism and one with undiagnosed decompensated hyperthyroidism and acute hepatitis. Two patients showed autoantibody reactivity which, together with liver histology, suggested the diagnosis of classic autoimmune hepatitis. Three patients experienced hepatotoxicity induced by propylthiouracil, the manifestations of which ranged from a benign course after drug withdrawal in one, a longstanding course in another suggesting drug-induced autoimmune hepatitis, and a more severe clinical condition with acute liver failure in a third patient, requiring liver transplantation. The three remaining patients showed no precipitating factors other than thyroid hyperactivity itself. They could be interpreted as having a thyroid storm with different clinical presentations. In conclusion, this series of patients illustrates the most frequent patterns of hepatocellular damage associated with hyperthyroidism and provides an algorithm for their diagnosis and treatment.

Keywords: autoimmune hepatitis; drug-induced hepatitis; liver function tests; thyroid disease; thyrotoxicosis hepatitis.

Figure 1

Case 3, showing cirrhosis with large septa and intense inflammation, a prominent interface, lobular activity, and hepatocyte rosetting (left, hematoxylin and eosin, 100×). Notes: At higher magnification, the numerous plasma cells and rosetting of hepatocytes are very conspicuous, in addition to the interface hepatitis (right, hematoxylin and eosin, 400×).

Figure 2

Case 6, with microscopic findings in the liver at autopsy. Notes: There is marked sinusoidal congestion and centrilobular necrosis (left, hematoxylin and eosin, 100×). Centrilobular necrosis is shown in detail at right (hematoxylin and eosin, 400×).

Figure 3

Case 8, in whom extensive areas of panacinar necrosis with variable inflammation (top left and top right, hematoxylin and eosin, 100×) was the dominant picture. Notes: In a few areas with more preserved parenchyma, there was bridge necrosis (bottom left, hematoxylin and eosin, 40×), and at higher magnification, numerous apoptotic bodies and mixed inflammation (bottom right, hematoxylin and eosin, 400×).

Figure 4

Algorithm for management of patients with symptoms of liver dysfunction and a previous diagnosis of hyperthyroidism. Abbreviation: PTU, propylthiouracil.