Hyperthyroidism-induced liver damage

　　Most scholars believe that liver damage in hyperthyroidism may be related to the following factors.

　　1, Toxic effects of thyroid hormones Thyroid hormones are mainly metabolized in the liver. Under physiological conditions, they directly (or indirectly) bind to receptors within liver cells without causing liver damage, but excessive intake can lead to liver damage. It was found early on that in cases of hyperthyroidism complicated with jaundice, bilirubin has congenital or acquired defects in transport from plasma to liver cells or binding within liver cells. This defect becomes apparent in clinical practice due to the presence of hyperthyroidism. Pathologically, mild to moderate cholestasis of liver cells, infiltration of eosinophils in the liver lobules, and proliferation of Kuffer cells can be seen, and it is believed that these changes are related to the increase in thyroid hormone levels.

　　2, Relative hypoxia and malnutrition of the liver During hyperthyroidism, the body's metabolism increases, and the oxygen consumption of visceral and tissue tissues increases significantly, but the blood flow to the liver does not increase, resulting in relative hypoxia of the liver; at the same time, vigorous metabolism reduces the synthesis of glycogen, protein, and fat while increasing catabolism, leading to excessive consumption of liver glycogen, essential amino acids, and vitamins, causing relative malnutrition of the liver. Both can lead to: (1) fatty degeneration of liver cells, manifested as liver enlargement; (2) with further exacerbation of hypoxia and malnutrition, the occurrence of liver cell necrosis, especially in the central area of the liver lobules, manifested as abnormal liver function, such as elevated serum transaminases, bilirubin, etc.; (3) continuous necrosis and regeneration of liver cells leading to liver fibrosis and even liver cirrhosis.

　　3, Heart failure and infection, shock Heart failure is relatively common in hyperthyroid cardiomyopathy, which can cause venous congestion in the liver, even central necrosis of the liver lobules, leading to liver damage, and even liver cirrhosis. Concurrent infection and shock can exacerbate liver damage.

　　4, Hyperthyroidism also affects the activity of various enzymes in the liver to varying degrees, thus affecting the body's metabolism. Videla LA et al. believe that hyperthyroidism can lead to Kuffer cell proliferation, an increase in serum aspartate aminotransferase (AST), exhaustion of reduced glutathione (GSH) in the liver, and a significant promotion of the formation of thiobarbituric acid-reactive substances (TBARS), resulting in an increased TBARS/GSH ratio (indicating the degree of liver oxidative stress response), and enhancing the chemiluminescence mediated by liver polysaccharides. The mechanism may be due to Kuffer cell proliferation, infiltration of polymorphonuclear leukocytes, increased activity of oxidative products of liver parenchymal cells, leading to an enhanced respiratory burst activity of macrophages.

　　5. During hyperthyroidism-induced liver damage, especially in the fatty degeneration of liver cells, it reduces the synthesis of TBG by the liver, leading to an increase in free thyroxine, enhancing its biological activity, and aggravating liver damage.

　　6. During hyperthyroidism, the blood flow and flow rate of arteries increase, and the pressure regulatory mechanism of the terminal branches of the hepatic artery and portal vein is destroyed, making it difficult to maintain the normal pressure within the liver. The peripheral sinusoids become congested and dilated, and then the blood pressure compresses the liver cells, causing liver atrophy.

　　7. Hyperthyroidism is an autoimmune disease with antibodies against self-organ antigens, which can be accompanied by other autoimmune diseases, such as myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, pernicious anemia, atrophic gastritis, etc. When complicated with primary biliary cirrhosis (PBC), it manifests as chronic non-suppurative inflammation of small intrahepatic bile ducts, persistent bile stasis, and ultimately as cirrhosis with不明显 regeneration nodules.

　　In addition to its clinical manifestations, hyperthyroidism-induced liver damage can also cause other diseases. The main complications of this disease include the following:

    1. Hyperthyroidism-induced liver damage often complicates with the aggravation of liver cell damage, resulting in liver enlargement, causing pain, presenting as dull pain.

　　2. Increased frequency of bowel movements.

　　3. Complications such as jaundice and deep yellow urine color

　　Hyperthyroidism-induced liver damage usually has no obvious characteristic manifestations, and it differs greatly from hyperthyroidism-induced heart disease, myopathy, and ophthalmopathy. The liver function can recover shortly after the control of hyperthyroidism; even if it is complicated with PBC, after antithyroid treatment, the liver function has varying degrees of improvement. The clinical symptoms of hyperthyroidism-induced liver damage are relatively mild, often manifested as mild digestive disorders, such as aversion to oil, anorexia, diarrhea, fatigue, discomfort or dull pain in the liver area, liver enlargement, and the examination finds tenderness or percussion pain in the liver area. It can also be without liver damage symptoms, only showing hyperthyroidism symptoms. Severe cases may appear jaundice, such as itching, yellow urine, conjunctival and general skin yellowing, enlargement of the liver and spleen, significantly abnormal liver function, and significant increase in alanine aminotransferase (ALT). Many scholars believe that hyperthyroidism-induced liver damage is closely related to patient age, course of disease, and condition, that is, hyperthyroidism-induced liver damage is more common in cases with a long course of hyperthyroidism, older age, and severe condition without reasonable treatment for a long time. Liver function examination should be paid attention to in older patients with longer course of disease and severe condition, and active liver protection treatment should be given if necessary.

　　The prevention of hyperthyroid liver damage should focus on the prevention and control of hyperthyroidism, while also supplementing liver protection treatment.

　　(1) Antithyroid treatment is mainly drug-based, propylthiouracil is the first-line drug for hyperthyroid liver damage, and for patients who are not suitable for thiourea drug treatment, β-receptor blockers such as atenolol can be used.

　　(2) For those with contraindications to thiourea drugs, 131 iodine radiotherapy and/or surgical treatment can be chosen.

　　(3) Stop using all drugs that damage the liver.

　　(4) Actively prevent and treat the complications of hyperthyroidism, such as heart failure, infection, and hyperthyroid crisis.

　　(5) Liver protection treatment, adequate rest, and strengthening nutrition. Adequate rest, and strengthening nutrition, can choose vitamins, amino acids, energy preparations, etc. If the diagnosis of hyperthyroid liver damage is timely and the treatment is active, the prognosis is good, and most patients recover within 2 months.

　　One Diagnosis The diagnosis of hyperthyroid liver damage is established if the following four conditions are met:

　　1. Based on typical clinical symptoms, signs, and thyroid function tests to confirm the diagnosis of hyperthyroidism.

　　2. Liver function tests should have one or more of the following: (1) ALT and AST elevated; (2) ALP elevated; (3) γ-GT elevated; (4) TB or (and) DB elevated; (5) Total protein or (and) albumin decreased; (6) Liver enlargement; (7) Jaundice.

　　3. Exclude liver function damage and liver enlargement caused by other reasons.

　　4. After the control of hyperthyroidism, liver function and liver enlargement return to normal.

　　Two Differential Diagnoses Hyperthyroid liver damage needs to be distinguished from hyperthyroidism complicated with viral hepatitis and hyperthyroidism complicated with drug-induced liver damage, although they all present with liver function damage, they have their own characteristics.

　　1. Medical history: The former can appear at any stage of the hyperthyroid course, with a relatively obvious history of epidemic diseases (such as close contact with hepatitis patients), unrelated to the severity of hyperthyroidism, while the latter is more common in patients who have not received regular antithyroid drug treatment for a long time or are mostly patients with severe conditions;

　　2. Symptoms: The former, in addition to hyperthyroid symptoms, has obvious symptoms of the digestive system (loss of appetite, aversion to greasy food, etc.), while the latter, even if there is liver damage, appetite is often not weakened and may even increase;

　　3. Laboratory examination: The former hepatitis virus markers are mostly positive, while the latter are mostly negative, which can be used as an important differential diagnosis basis.

　　1. High calorie:Determined by the clinical treatment needs and the patient's eating habits, generally increased by 50%-70% compared to normal, and each person can provide 3000-3500Kcal of calories per day.

　　2. High protein:Hyperthyroid patients have a vigorous metabolism and have a significant increase in the demand for nutrients. If nutritional supplementation is insufficient, weight loss will be more obvious, and generally, each person needs 1.5-2g of protein per kilogram of body weight per day. Young patients also need to eat more fatty foods.

　　3. High vitamin:Mainly supplement B vitamins and vitamin C. Eat more fruits and vegetables rich in vitamins,

　　4. Appropriate minerals:Mainly potassium, magnesium, calcium, etc.

　　5. Avoid iodine:Hyperthyroid patients should avoid high-iodine diet or iodine-containing drugs, but they can eat iodized salt daily!

　　Mild hyperthyroidism liver damage is not an indication for discontinuation of antithyroid drugs. If the patient's appetite is normal and there is no jaundice, the medication can still be continued. The dose of antithyroid drugs is slightly reduced, about 2/3 to 3/4 of the general dose, such as methimazole or propylthiouracil, the conventional daily treatment dose is 30 mg and 300 mg respectively, at this time the dose can be reduced to 20 mg and 200 mg per day. At the same time, add liver-protecting drugs, such as 3 tablets of Glucuronolactone once, three times a day; and/or 3 tablets of liver-protecting tablets once, three times a day. Closely observe the patient's appetite, weight, jaundice, and changes in transaminases. At the same time, strengthen nutrition, the majority of patients' transaminases will improve.

　　Some scholars believe that the main cause of hyperthyroidism liver damage is autoimmune damage, so it is recommended to use corticosteroids as early as possible in treatment. For patients with mild liver damage, small doses of corticosteroids should be added while reducing the dose of antithyroid drugs. That is to say, while continuing to use methimazole or propylthiouracil (20 mg and 200 mg per day respectively), 15-30 mg of prednisone should be given daily. While using corticosteroids, potassium, calcium, and other supplements should be taken. Potassium chloride 0.5-1 gram per time, three times a day, Caltrate D600 one tablet per day, active vitamin D, such as Rocaltrol one tablet per day.

　　For patients with severe liver damage, the author recommends using corticosteroids as the main treatment drug, and using antithyroid drugs after liver function returns to normal. It is also recommended that patients be hospitalized for treatment. In the selection of antithyroid drugs, if liver function abnormalities are mainly due to elevated liver enzymes, methimazole is recommended; if liver function abnormalities are mainly due to cholestasis, propylthiouracil is recommended.

　　Hyperthyroidism liver damage should be paid attention to. During the initial visit and treatment process, especially in the first 4 months before treatment, liver function should be monitored. If liver damage treatment is active and proper, the prognosis is good.