Case 1
A 52-year-old male patient was diagnosed with GD 20-years ago with history of heat intolerance, sweating, weight loss, tremors, increased appetite, accompanied by change in temperament, and exophthalmos. The patient was put on a treatment with anti-thyroid drug (ATD) propylthiouracil, methimazole and prednisolone which brought an improvement of the symptoms, exophthalmos, and thyroid function. However, some 5-years ago, he noticed an enlargement of the thyroid and 6-months later, he complained of persistent profuse sweating, heat intolerance, palpitation, associated with neck pain, mild breathing difficulty, there were no significant weight loss and no significant increase in bowel movements. He was put on methimazole (10 mg bid), which proved ineffective. He denied having any history of smoking, alcohol or drug abuse. There was no significant past medical or surgical history.
He was admitted in our department in July 2012 and upon physical examination, his blood pressure was 120/82 mmHg, and heart rate of 98/min regular. He had moist skin, tremors, bilateral moderate exophthalmos of mean and no pedal oedema. His thyroid showed a bilateral 3rd degree enlargement, soft in consistency, non tender, no palpable nodules and no bruits upon auscultation. Thyroid ultrasonography showed bilateral enlargement of the thyroid gland and radioactive iodine uptake test showed a significantly elevated thyroid
123I uptake function at 2 and 24 hours of 95.7% and 71.4% respectively. Orbital CT showed bilateral exophthalmos; the prominence was of 19.0 mm and 19.3 mm Hertel readings on the right and left sides respectively, abdominal ultrasound showed no abnormalities. Blood chemical tests documented normal renal function and hepatic values but revealed a significant increase in serum thyroid hormone levels (Table
1). The possibility of primary liver disease could be ruled out; there was no evidence of immunological conditions (autoimmune hepatitis, primary sclerosing cholangitis or primary biliary cirrhosis); neither was metabolic liver disease due to alpha-1 antitrypsin deficiency, hemochromatosis or Wilson´s disease identified. Hepatitis serology was negative and serology for several other virus infections that might lead to liver dysfunction did not indicate presence of active virus infection. The patient´s alcohol consumption was sparse limited to less than one drink a month. Grave’s hyperthyroidism was diagnosed and the treatment dosage for the patient was determined by the intake rate and the size of thyroid gland. If the dosages is over 10 mCi
131I, the patients will be treated in two divided doses of 5–7 mCi each to minimise side-effects.
Table 1
Chronological thyroid function test and liver function test for case 1
Event
|
fT3
|
fT4
|
TSH
|
Tb
|
AST
|
ALT
|
AKP
|
δ
GT
|
ALB
|
3.5-6.5 pmol/L | 10.2-31.0 pmol/L | 0.35-5.53 mU/L | 3.4-17.1 Umol/L | <40 U/L | <58 U/L | 40–130 U/L | <60 U/L | 34–48 g/L |
1ST admission 2012-07-11 | 30.0 | 84.0 | 0.02 | 15.1 | 26.1 | 32.8 | 121.5 | 44.6 | 42.0 |
2012-07-25 1st Dose of RAI
|
7-days post-RAI dose 1 2012-07-31 | | | | 28.0 | 68.0 | 186.0 | 96.0 | 127.0 | 30.0 |
After 1-week of liver protection treatment 2012-08-06 | | | | 19.4 | 25.9 | 54.0 | 95.4 | 107.5 | 32.0 |
2012-09-02 2nd Dose of RAI
|
2nd Admission 2012-09-14 | 30.0 | 128.0 | 0.01 | 44.1 | 29.0 | 27.9 | 148.6 | 152.6 | 30.0 |
After 12-days of liver protection treatment 2012-09-25 Discharge | 30.0 | 112.0 | 0.24 | 88.5 | 26.9 | 58.1 | 137.1 | 90.8 | 32.0 |
7-days after the first RAI dose of 5 mCi, the patient’s blood chemical tests revealed an abnormal liver function (Table
1), the abdominal ultrasound showed no abnormalities. The patient was treated with Essentiale Forte N®
[
5] (Polyene Phosphatidyl Choline) and Bicyclol®
[
6] for liver protection and prednisolone (30 mg qd).
One week later, the blood investigations showed marked recovery from the liver failure (Table
1).
About 5-weeks following the first RAI dose, the patient was subjected to his second dose of 5 mCi. 2-weeks following the second RAI dose, the patient presented to our department complaining of discomfort in the right upper quadrant, loss of appetite, palpitation and light coloured stools.
Upon admission, the blood tests revealed marked liver dysfunction (Table
1). Abdominal ultrasound showed no abnormalities. The patient was diagnosed with hepatotoxicity following the administration of a dose of RAI. The treatment regimen was aimed at liver protection with injections of Samyr®
[
7] (ademetionine-1, 4-butanedisulphonate) and Tianqing Ganmei®
[
8] (magnesium isoglycyrrhizinate); intravenous Vitamin C
[
9] administration, prednisolone (30 mg qd) and Leucogen®
[
10] (asparaginase) to raise the white cell count.
The liver toxicity was resolved within 10-days (Table
1). Upon discharge, the thyroid function test showed (Table
1). In an outpatient review, 2 months later, the patient thyroid function proved to be euthyroid and the liver function remained on the normal side.
Case 2
A 34-years-old female patient was diagnosed 10-years ago with GD with history of tremors, heat intolerance, sweating, weight loss, increased appetite, irritability, increased stool frequency and reduced menstrual flow and was put on methimazole (5 mg qd). The patient self-discontinued the treatment and upon review, the thyroid hormones showed normalisation.
1-year after the discontinuation of medication, there was a relapse and the patient was admitted to her treating-hospital at the time. Upon discharge, the patient was put back on methimazole (2.5 mg qd). 10-months ago, the patient attended our out-patient department for review. The thyroid hormone levels showed a normalisation and the treating physician advised to stop all medications.
12-days following the discontinuation of treatment, the patient observed a recurrence of palpitation and tremors. The patient was referred to our department for a thyroid function test and the blood chemical tests documented normal renal function and hepatic values but revealed a significant increase in serum thyroid hormone levels (Table
2). A relapse of Grave’s hyperthyroidism was diagnosed and 2 days later, she was admitted as in-patient for treatment with RAI. The patient had good mental health, good sleeping pattern, good appetite, normal bowel frequency, normal urine and no significant recent weight change. She had no history of taking iodine-containing drug and no history of throat or neck pain. The possibility of primary liver disease could be ruled out; there was no evidence of immunological conditions (autoimmune hepatitis, primary sclerosing cholangitis or primary biliary cirrhosis); neither was metabolic liver disease due to alpha-1 antitrypsin deficiency, hemochromatosis or Wilson´s disease identified. Hepatitis serology was negative and serology for several other virus infections that might lead to liver dysfunction did not indicate presence of active virus infection. The patient´s alcohol consumption was sparse limited to less than one drink a month.
Table 2
Chronological thyroid function test and liver function test for case 2
Event
|
fT3
|
fT4
|
TSH
|
Tb
|
AST
|
ALT
|
AKP
|
δ
GT
|
ALB
|
3.5-6.5 pmol/L | 10.2-31.0 pmol/L | 0.35-5.53mU/L | 3.4-17.1 Umol/L | <40 U/L | <58 U/L | 40–130 U/L | <60 U/L | 34–48 g/L |
1st admission 2011-12-05 | 16.67 | 53.15 | 0.02 | 4.8 | 37.0 | 52.0 | 58.0 | 26.0 | 75.0 |
2011-12-08 Dose of RAI
|
2nd admission 2011-12-15 | 11.42 | 40.21 | 0.01 | 28.4 | 407.0 | 796.0 | 168.0 | 188.0 | 40.0 |
After 13-days of liver protection treatment 2011-12-28 Transfer to hepato-biliary department | 9.38 | 44.1 | 0.09 | 130.8 | 59.0 | 29.0 | 111.0 | 54.0 | 38.0 |
Upon examination, she had 2nd degree bilateral thyroid enlargement, soft in consistency, non tender, no palpable nodules and no thyroid bruit on auscultation. Chest X-ray was normal, abdominal ultrasound showed no abnormalities, orbital CT showed bilateral exophthalmos; the prominence was of 19.1 mm and 18.8 mm Hertel readings on right and left sides respectively. Thyroid scan showed bilateral lobe swelling and radioactive Iodine uptake test showed a significantly elevated thyroid 123I uptake function at 2 and 24 hours of 40% and 59.0% respectively. She received RIT (10 mCi) and was discharged the following day on 30 mg of prednisolone per day.
5-days following the RAI treatment, the patient started complaining of a mild sense of nausea; she underwent serological investigations, which pointed towards a hepatic dysfunction (Table
2). The patient was readmitted, her liver function test showed hepatotoxicity (Table
2), abdominal ultrasound did not show any abnormal finding and the following treatment was administered: Atomolan®
[
11] (reduced glutathione tablets), Essentiale Forte N®
[
5] (polyene phosphatidyl choline injection) and Bifendate®
[
12] as liver protective treatment, prednisolone (30 mg qd) and Leucogen®
[
6] (asparaginase) to raise white blood cells.
13-days after the second admission, despite the intensive hepato-protective treatment, the patient’s liver function markers remained elevated with the exception of the alanine aminotransferase (ALT) (Table
2). The patient was eventually transferred to the Hepato-biliary department to continue her intensive treatment. 3-weeks later, her liver function tests were back to normal and she was ultimately discharged from the Hepato-biliary department. Till date, the liver function is normal and she is currently euthyroid.