ABSTRACT
The potencies of resorcinol, 6-propylthiouracil (PTU) and methimazole (MMI) for inducing developmental toxicity and neurotoxicity were compared in pregnant rats, regarded as valid model for human thyroid toxicity. Profound differences on maternal thyroid hormone levels (THs), maternal toxicity as well as developmental and neurotoxicity sequelae occurred. Resorcinol affected none of those end points. PTU and MMI caused significant effects. Therapy with either PTU or MMI during the first trimester of human pregnancy can cause reductions of maternal THs, accompanied by disruptions of prenatal development. Clinical MMI studies show sporadic evidence of teratogenic effects, with equivocal relation to thyroid peroxidase (TPO) inhibition. In recent decades no MMI associated prenatal toxicity has been reported, an outcome possibly related to carefully managed therapy. Orally administered resorcinol was rapidly absorbed, metabolized and excreted and was undetectable in the thyroid. In contrast, PTU or MMI accumulated. Resorcinol's potency to inhibit TPO was profoundly lower than that of PTU or MMI. Quantum chemical calculations may explain low resorcinol reactivity with TPO. Thus, distinctions in the target organ and the TPO inhibitory potency between these chemicals are likely contributing to different reductions of maternal THs levels and affecting the potency to cause developmental toxicity and neurotoxicity.
Subject(s)
Enzyme Inhibitors/toxicity , Iodide Peroxidase/antagonists & inhibitors , Iron-Binding Proteins/antagonists & inhibitors , Methimazole/toxicity , Propylthiouracil/toxicity , Resorcinols/toxicity , Thyroid Gland/drug effects , Abnormalities, Drug-Induced/etiology , Administration, Oral , Animals , Autoantigens/metabolism , Biomarkers/blood , Dose-Response Relationship, Drug , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/metabolism , Female , Gestational Age , Humans , Iodide Peroxidase/metabolism , Iron-Binding Proteins/metabolism , Methimazole/administration & dosage , Methimazole/metabolism , Neurotoxicity Syndromes/etiology , Pregnancy , Propylthiouracil/administration & dosage , Propylthiouracil/metabolism , Rats , Resorcinols/administration & dosage , Resorcinols/metabolism , Risk Assessment , Thyroid Gland/enzymology , Thyroid Hormones/bloodABSTRACT
A 16-year-old male with language disorders, such as motor aphasia or mutism, was hospitalized on day 4 after the onset of fever. Magnetic resonance imaging (MRI) on admission revealed lesions of the corpus callosum and brain white matter. Brain single photon emission computed tomography (99mTc-ethyl cysteinate dimer) on day 7 shows hypoperfusion (with right dominance) of bilateral upper parietal region. His condition improved gradually with symptomatic treatments alone, and he was discharged on day 13. The lesions on the MRI disappeared by day 15. Although this case might have suffered from leukoencephalopathy, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) type II was suspected from the reversible splenial lesion. Except for the elevation (640 times) of mycoplasma pneumonia antibody titer (particle agglutination) in the serum, the blood tests and cerebrospinal fluid findings showed no significant abnormalities. We then considered this encephalopathy was related to mycoplasma pneumonia infection. Since no symptoms of mycoplasma infection except for neurologic symptoms were observed, indirect mechanism, such as immune-mediated reactions, is suggested to cause encephalopathy in this case.
Subject(s)
Encephalitis/diagnosis , Encephalitis/microbiology , Pneumonia, Mycoplasma , Adolescent , Brain/diagnostic imaging , Diagnosis, Differential , Humans , Leukoencephalopathies , Magnetic Resonance Imaging , Male , Severity of Illness Index , Tomography, Emission-Computed, Single-PhotonABSTRACT
A 75-year-old woman with no significant medical history was admitted to our hospital with congestive heart failure. Echocardiography revealed left ventricle (LV) systolic dysfunction [LV ejection fraction (LVEF) 18%] and diffuse LV hypokinesis mimicking dilated cardiomyopathy. Her brain natriuretic peptide (BNP) level was elevated (1214.3 pg/mL). Standard medications for heart failure failed to ameliorate her cardiac failure symptoms. Echocardiography on admission revealed thickening of the basal interventricular septum without morphological changes. Cardiac magnetic resonance imaging showed late enhancement in the epicardial side dominance of the LV at the late phase. Lysozyme and soluble interleukin 2 receptor levels were elevated. No abnormalities were found in the lungs, eyes, or skin, and she was diagnosed with cardiac sarcoidosis. At 23 days after beginning treatment, the patient received oral steroid therapy (prednisolone 30 mg/day) along with standard heart failure medications. The dose was tapered by 5 mg at 4-week intervals and then maintained at 10 mg per day. At 17 days after initiating steroid therapy, her BNP value decreased and remained at a low level. Echocardiography showed improvement of the LV dimensions and LVEF. In patients with severe LV dysfunction diagnosed with cardiac sarcoidosis, we propose that careful steroid therapy be considered, even for elderly patients.