OBJECTIVETo investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats.

METHODSHypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting.

RESULTSignificantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001).

CONCLUSIONThe intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.

Animals ; Animals, Newborn ; Apoptosis ; physiology ; Female ; Hippocampus ; pathology ; Hypothyroidism ; chemically induced ; pathology ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications ; pathology ; Propylthiouracil ; Rats ; Rats, Wistar

Amiodarone is a di-iodated benzofuran derivative that is commonly used to treat patients with various cardiac arrhythmias. It is associated with side effects that involve the liver, thyroid, and other organs. Approximately 1-3% of patients treated with amiodarone suffer from symptomatic liver disease. Thyroid dysfunction occurs in 10% of patients treated with amiodarone. A 65-year-old woman with coronary heart disease and atrial fibrillation was administered with amiodarone. She developed nausea, vomiting, dyspepsia, and sweating within 9 months of amiodarone administration (200 mg orally once a day). Results of the laboratory finding showed increased hepatic enzymes, and low thyroid hormone levels. A liver biopsy showed irregular arrangement of hepatocytes and diffuse micro- and macrovesicular fatty changes. Electron microscopy findings showed pleomorphic mitochondria with crystalloid inclusions and membrane-bound lysosomal structures. The liver and thyroid functions returned to normal, after the amiodarone was stopped. We describe an unusual case in which amiodarone induced hepatitis and hypothyroidism simultaneously. Physicians should take a close look to the adverse event when using amiodarone which can cause adverse effects in multiple organs.
Aged ; Amiodarone/*adverse effects/therapeutic use ; Arrhythmias, Cardiac/drug therapy ; Drug-Induced Liver Injury/*complications/pathology/*radiography ; Female ; Fibrosis/pathology ; Humans ; Hypothyroidism/*chemically induced/*complications ; Microscopy, Electron ; Mitochondria/drug effects/metabolism ; Tomography, X-Ray Computed ; Treatment Outcome

OBJECTIVETo comprehensively evaluate the treatment of Graves' disease in children with (131)I and antithyroid drugs (ATD) and to quantitatively assess the advantages and disadvantages of them.

METHODSThe authors examined the outcome of (131)I and ATD treatment in children with Graves' disease at the Hospital of Dongshan District in Guangzhou during the period 1997 to 2002. Each of the 2 groups of patients consisted of 40 patients ranging in age from 8 to 14 years (mean 10.7 +/- 2.2). The groups were similar in age, gender, length of disease, goiter size, and initial serum thyroid hormone levels. Thyroid status was assessed > 2 year after the therapies started. The efficacy of the therapeutic methods were scored as follows: the children whose disease was cured were marked 0, and those who had improvement but were not cured were marked 1, and those who remained unchanged were marked 2. After treatment the patients who were demonstrated to have ophthalmopathy or more severe ophthalmopathy, hyperthyroid heart disease, liver function damage and leukopenia were marked 2 respectively, and those who showed temporary hypothyroidism and permanent hypothyroidism were marked 1 and 2, respectively. Those who had a relapse of the disease after being cured were marked 2. The effects of two groups and total scores were compared.

RESULTSThe total score of the group treated with (131)I was 34; and the median score was 1; the total score of the group treated with ATD was 69, and the median score was 1.5; the difference between the two groups was statistically significant (P < 0.01). When these two groups were compared, the advantage of (131)I in the treatment of this disease was clear. The incidences of ophthalmopathy and improvement of ophthalmopathy of the two groups were not significantly different (P > 0.05). No significant difference was found in incidence of hypothyroidism between the two groups (P > 0.05). There was no significant worsening or new development of ophthalmopathy or hypothyroidism after (131)I and ATD treatment. The rate of relapse of hyperthyroidism among patients cured with (131)I was significantly lower than that among patients cured with ATD (P < 0.05). In the patients treated with (131)I the incidences of hyperthyroid heart disease, liver function damage, leukopenia and so on were significantly lower than those of patients treated with ATD (P < 0.05).

CONCLUSIONS(131)I therapy was superior to the ATD in treatment of the children with Graves' disease. Observations for more than 2 years after treatment with (131)I showed that there were no harmful side effects or complications. (131)I can be recognized as the safer, more convenient and effective treatment than ATD for Graves' disease in children.

Adolescent ; Antithyroid Agents ; adverse effects ; therapeutic use ; Child ; Female ; Graves Disease ; complications ; drug therapy ; radiotherapy ; Graves Ophthalmopathy ; drug therapy ; radiotherapy ; Humans ; Hyperthyroidism ; drug therapy ; radiotherapy ; Hypothyroidism ; chemically induced ; Iodine Radioisotopes ; adverse effects ; therapeutic use ; Male ; Secondary Prevention ; Severity of Illness Index ; Treatment Outcome