Mirza Naqi Zafar ( Laboratory, Dr. Ziauddin Hospital, Karachi. )
Syed Jamiluddin Rizvi ( Laboratory, Dr. Ziauddin Hospital, Karachi. )
Serajuddaula Syed ( Laboratory, Dr. Ziauddin Hospital, Karachi. )
Thyroid hormone levels were estimated in fifty patients with hepatitis B. In acute phase, 13 was raised in 10% and T4 in 60%. This rise was directly proportional to the transaminases levels. Twenty cases were also studied in the recovery phase where thyroid hormones returned to within normal limits. This rise of 13 and 14 in acute phase is attributed to increased thyroxin binding capacity due to release of thyroid binding globulin Into circulation from necrosing hepatocytes (JPMA42: 56, 1992).
The liver plays a central role in metabolism of the thyroid hormones. It produces the main transport protein, thyroxin binding globulin (TBG), which binds 75% of the circulating hormone1. Deiodination of T4 to T3 occurs mainly in the liver2. This process thus initiates both action and catabolism of the hormones. Conjugation, deamination and decarboxylation of side chains of T3 and T4 also occur in the liver3,4. In chronic liver disease, abnormalities of thyroid function are well established. There is reduced conversion of T4 to T3 and low levels of FT3 and FT45,6. However, there are conflicting reports on thyroid status in acute viral hepatitis7-9.. This has been attributed to heterogeneity of population studied in terms of type and severity of hepatitis infection. We have, therefore, studied thyroid hormone levels in hepatitis B in both acute phase and clinical, biochemical recovery phase, to assess the status of thyroid hormone profile in clinically euthyroid individuals.
PATIENTS AND METHODS
Fifty cases of serologically diagnosed hepatitis B (HBs Ag and anti HBc IgM positive) were studied in the acute phase of infection. Thyroid hormones T3, T4 and TSH were estimated by Elisa kits (Boehringer). Liver function tests (bilirubin, alkaline phosphatase, ALT and AST) were done on Hitachi 705 autoanalyser. Of 50 cases initially studied, 30 were lost to follow-up. Thus thyroid hormones assays and LFTs were done in the recovery phase in 20 cases, three weeks later. Ml the fifty cases were clinically euthyroid. Normal ranges reported for thyroid hormones were predetermined in our laboratory on 100 normal healthy individuals. Statistical analysis included \\\'t\\\' test and correlation coefficient10,11.
In the fifty cases of hepatitis B infection studied in the acute phase, 174 was raised in sixty percent and T3 in ten, while TSH was within normal limits. In twenty cases, where follow-up was possible in the resolved phase, all parameters were within normal limits. Significant reduction in 174 values was observed in the resolved phase as compared to acute phase while T3 reduction was nonsignificant. LFTs were significantly reduced in the resolved phase (Table I).
Patients studied in the acute phase were divided into two groups, (a) with abnormal and (b) with normal thyroid profiles. In group A T3 andT4 or both were raised. MeanT3 was within normal limits while T4 was far beyond normal limits. Transaminases AST and ALT, ALP and bilirubin were markedly raised. In group B thyroid hormones were within normal limits and liver functions were half of those in group A (Table II).
Attempts were made to correlate T3 and T4 levels with those of enzymes AST and ALT. Correlation was nonsignificant for T3 till enzymes levels were beyond 1000 U/L However for 174, significant correlation was observed from values beyond 500 U/L (Table III).
This study shows that in clinically euthyroids with acute hepatitis B virus infection, there is rise of serum T3 in 10% and T4 in 60% of the patients respectively. This rise is proportional to the extent of hepatocyte necrosis as shown by jaundice and high transaminases in those patients where T3/T4 were raised when compared to those with normal thyroid functions. Furthermore, correlation of rise of T3/T4 and increased values of transaminases is significant in extensive hepatic cell death, i.e., enzymes beyond 1000 U/L levels. Earlier reports agree with our findings when one considers the rise of T49 However, no report shows rise of T3 values7-9. This rise of Li has been attributed firstly due to release of thyroid binding globulin into circulation as a result of hepatic cell death and secondly to reduced conversion ofT4 to T39. This may be a valid explanation in severe cases of hepatitis and not in mild to moderate cases where no alteration of thyroid hormones was observed. We report rise of T3 while others have not seen any rise of T3 and in fact reported reduction of FT39 Consideringthe conjugation of T3 and T4, we know that Li preferentially forms glucoronides while T3 conjugates to sulphate. Both are excreted in bile while the former can also be found in the systemic blood4. It is possible that the released TBG binds this conjugate Li, raising serum T3. Since the patients are clinically euthyroid, the rise of T3/T4 is due to the increased binding capacity of serum specially when TSH levels are unaltered. This is further supported by the fall of T3/T4 in the recovery phase. Thyroid hormone profile can thus be a good index of severity of cell death and of value in predicting the future course of the disease process. This is specially so when we know that progression of liver disease to the chronic phase causes disturbances of the thyroid hormone metabolism5,6.
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