Spontaneous occlusion of the circle of Willis (moyamoya syndrome).

Three young autopsy and four temporal artery biopsy cases with an arteriographically typical moyamoya syndrome were studied by histologic, electron microscopic, and immunofluorescence methods. In all autopsy cases the intracranial segment of the internal carotid arteries showed concentric intimal thickening with severe stenosis or obstruction of the lumen, folding of the internal elastic lamina, and shrinkage of the external diameter of the vessel. Inflammatory infiltration was absent. Abnormal networks of thin-walled vessels, interpreted as secondary collaterals, were seen at the base and on the convexity of the brain. Degenerative changes, including a ruptured coronary aneurysm in one case, were also noted in the coronary and temporal arteries. In both the intra- and extracranial arteries repeated endothelial damage was indicated by the presence of redundant subendothelial basement membrane-like material. Lipid or calcium deposits were exceptional, and no evidence for the presence of immunoglobulins or components of the complement could be obtained by immunofluorescence. These pathologic alterations, distinct from atherosclerosis, fibromuscular dysplasia, and the established types of arteritis, seem to be identical in children and adults, in spite of different clinical manifestations of the moyamoya syndrome in these age groups. We suggest that a humoral factor, associated with infections, may induce repeated endothelial damage and intimal thickening in the intracranial arteries of genetically predisposed children in analogy with recent observations made in the coronary arteries of young subjects.

Thyroxine, triiodothyronine, and thyrotropin in serum during long-term diphenylhydantoin therapy.

Clinical laboratory tests for assessment of thyroid function were performed in 31 patients receiving long-term diphenylhydantoin (DPH) therapy. Reduced serum total thyroxine and free thyroxine index were found. The decrease in serum total triiodothyronine and free triiodothyronine index was smaller but statistically significant. DPH had no significant effect on the serum thyrotropin (TSH) concentration and maximal TSH response to TSH-releasing hormone. The absence of reciprocal changes in TSH and serum thyroxine might be due to the near-normal triiodothyronine concentration. Such an explanation would also conform with previous findings that the pituitary contains specific receptors for triiodothyronine but not thyroxine.

Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs.

Thyroid function tests were studied in patients undergoing long-term treatment with various anticonvulsant drugs. Previous reports that diphenylhydantoin induces a decrease in the serum concentrations of total and free thyroxine (T4) and triiodothyronine (T3) without a change in the TSH concentration were confirmed. Diphenylhydantoin had no effect on reverse T3. Carbamazepine was also found to decrease serum T4, the free T4 index and T3 but, with the exception of T3, the decrease was smaller than that induced by diphenylhydantoin. Dipropylacetic acid did not influence the serum thyroid hormone concentrations, and neither did primidone. This demonstrates that the interaction between anticonvulsant drugs of different chemical structure and thyroid hormone metabolism is diverse. None of the drugs tested altered serum TSH or the T3 uptake test for the estimation of unsaturated thyroid hormone binding-capacity in serum. These two tests are considered diagnostically more dependable than the measurement of thyroid hormones in serum when diphenylhydantoin and carbamazepine are administered.

Free thyroxin and free triiodothyronine as measured by equilibrium dialysis and analog radioimmunoassay in serum of patients taking phenytoin and carbamazepine.

We measured free thyroxin (FT4) and free triiodothyronine (FT3) in serum of patients taking the anti-epileptic drugs phenytoin and carbamazepine, both by equilibrium dialysis procedures and analog-type radioimmunoassays. By either assay, the mean concentration of FT4 was significantly decreased in patients receiving either drug, whereas their FT3 concentrations were normal or only slightly decreased. Adding therapeutic concentrations of these drugs in vitro to control sera had a small or no incremental effect on FT4 and FT3 as measured by either method, but adding greater concentrations of the drugs in vitro markedly increased the concentrations of the free hormones. These results indicate that the main mechanism of the decrease in concentrations of free thyroid hormones in serum during therapy with anticonvulsant drugs is not the displacement of hormones from their binding to plasma proteins. We also determined, using a new and sensitive immunoradiometric assay, that patients taking carbamazepine, but not those taking phenytoin, had significantly less thyrotropin in the serum.

Effect of anticonvulsant and antidepressant drugs on iodothyronines in serum.

Serum iodothyronine concentrations were measured in patients on long-term therapy with one or two anticonvulsant drugs. Diphenylhydantoin (DPH) and carbamazepine (CBZ) reduced the serum levels of thyroxine (T4) free T4 index, reverse triiodothyronine (rT3) and 3,3'-diiodothyronine (3,3'-T2), whereas the depressant effect on the serum levels of triiodothyronine (T3) and free T3 index was small but statistically significant. In patients administered DPH and phenobarbital (PB) or CBZ and primidone (PD) the serum iodothyronine levels were also depressed, except for normal T3 and free T3 index. Patients receiving only PB or PD had normal serum levels of total and free thyroid hormones, but decreased concentrations of rT3 and 3,3'-T2. Only supratherapeutic concentrations of DPH and CBZ added in vitro to control sera significantly reduced the number of T4 and T3-binding sites, as reflected in increased T4 and T3 uptake test results. This indicates that the DPH and CBZ-induced decrease in thyroid hormone concentrations in vivo is not due to a displacement of thyroid hormones from their binding sites on serum proteins. The antidepressant drugs amitriptyline and mianserin had no effect on the thyroid hormone levels in serum.