In 14 patients with overt primary hypothyroidism, we examined visual fields by Goldmann's isopter perimetry. An unexpectedly high incidence (10 patients, 71.4%) of visual field defects was found. Two patients complained of visual failure, whereas 12 had no subjective symptoms. The extent of visual field change varied over a wide range, from early chiasmal compression to apparent bitemporal hemianopsia. The abnormality was characteristically restriction in the central visual field; peripheral vision was less often affected. The sella turcica was significantly enlarged in these patients as compared to controls. The volume of the sella turcica correlated significantly with both basal serum TSH and total pituitary reserve of TSH (r = 0.82, P less than 0.001). There was no correlation between the extent of visual field change and the volume of the sella turcica or pituitary TSH reserve. Of 10 patients with visual field defects, 8 improved during 1-4 months of T4 replacement. In 2 patients, however, the visual field defect deteriorated during replacement. The deterioration occurred when serum TSH levels had decreased to about 50% and 20% of pretreatment values, respectively. The peak serum TSH after TRH stimulation was higher at the time of deterioration than before treatment. Visual fields became normal during treatment with an increased dose of T4 (200 micrograms/day), when serum TSH was suppressed to an undetectable level. The paradoxical course of visual failure during T4 replacement may be due to an imbalance between TSH synthesis in the pituitary and TSH release which may induce an increase in pituitary size. The data suggest that visual field defects and their deterioration are due to pituitary hyperplasia and are reversible with T4 replacement. In order to rule out a pituitary tumor, hypothyroid patients with visual failure should be followed during T4 replacement therapy.

The manner of inhibition of thyroid I \ m=-\accu-mulation by perchlorate (ClO4\m=-\) and thiocyanate (SCN\m=-\) was studied using a newly developed biological model of the I\m=-\ transport system. ClO4\m=-\inhibited I\m=-\accumulation in phospholipid vesicles made from thyroid plasma membrane and soybean phospholipids by decreasing Na+\x=req-\ dependent I\m=-\influx. The anion did not at all induce I \ m=-\ leakage from the vesicles. On the basis of Lineweaver\x=req-\ Burk plot analysis, it did not change Vmax for I \ m=-\concen-tration. These results suggest that ClO4\m=-\is a competitive inhibitor of thyroid I \ m=-\ transport.

The I- transport system in the thyroid plasma membrane (PM) was successfully reconstituted in phospholipid vesicles (P-vesicles) by sonication. P-vesicles thus prepared were able to concentrate I- in the presence of external Na+. The activity of the I- transport increased with increase in the Na+ concentration outside the P-vesicles and with graded doses of PM protein used for the reconstitution in P-vesicles. When P-vesicles were prepared with only the lipid components extracted from PM instead of total PM, they were deprived of the biological activity to accumulate I-. Methimazole (MMI) did not change the Na+-dependent I- transport, but ClO4- and SCN- had inhibitory effects on the transport. These observations indicate that 1) a specific I- translocator is present in the thyroid PM, 2) the translocator is easily reconstituted in P-vesicles, 3) the translocator may not consist of phospholipids despite the theory of the I -concentrating thyroid phospholipids, and 4) Na+-I- cotransport through the translocator may be the mechanism for the accumulation of I- in the thyroid cells.

A 32-yr-old man with goitrous hypothyroidism due to an iodide-trapping defect is described. He was admitted because of goiter which had been increasing in size. His parents were unrelated, and no cases of goiter were found in his family. On admission, serum T3 was 39 ng/dl, serum T4 was 1.0 micro g/dl, and serum TSH was 217 micro U/ml. His 24-h thyroidal 131 I uptake was 0.05%. Antithyroid antibodies were negative. In a tracer study, the thyroidal 131 I uptakes were 6.3% at 2 h, 4.0% at 6 h, and 0.9% at 24 h after iv injection of the radioiodide. The decline in the neck counts was linear and parallel to that in the serum 131 I. The 24-h urinary excretion of 131 I was 92%. The saliva to serum and gastric juice to serum ratios of 131 I concentrations at 2 h were very low (0.95 and 0.97, respectively). After the administration of iodine (14 mg in Lugol's solution/day for 10 days), serum T3 was 228 ng/dl, serum T4 was 6.8 micro g/dl, and serum TSH was 24 micro U/ml. Some biochemical studies were carried out using the patient's thyroid tissue. In a kinetic study on iodide trapping by thyroid slices, the thyroid to medium ratio of iodide concentration in the patient's tissue was constantly about 0.1, in contrast to 1.5-4.0 in a control subject. The microsomal peroxidase activity in the patient's thyroid, assessed by iodination of bovine serum albumin, was about 3-fold that in a control subject on the basis of DNA content. Both ouabain-sensitive and -insensitive thyroidal Na+ -K+ -ATPase activities were present. These results suggest that the iodide-trapping defect in this patient was due to an impairment in the specific iodide carrier system rather than in the Na+ -K+ -ATPase itself.

Some biochemical characteristics of the thyroid I- translocator and of I- accumulating phospholipid vesicles (P-vesicles) were studied. P-vesicles were made from thyroid plasma membranes (PM) and soybean phospholipids by sonication. The optimal incubation temperature for Na+-dependent I- accumulation in P-vesicles was from 18-26 C. Only a small amount of Na+-independent I- accumulation was observed at various incubation temperatures, but it increased in proportion with the temperature up to 36 C. The optimal incubation pH (7.0-7.5) was near the physiological extracellular pH. When PM were heated at 55 C for 30 min before preparation of P-vesicles, Na+-dependent I- accumulation in the vesicles decreased by 35%. When they were heated at 65 C for 30 min, the I- -accumulating activity was almost completely lost. The translocator was also inactivated when PM were sonicated at 37 C in the presence of trypsin. The internal and external administration of ouabain to the vesicles did not affect the activity of Na+-dependent I- accumulation. When PM were treated with sodium dodecyl sulfate at a final concentration of 0.2-0.6 mg/ml, the I- translocator was inactivated or detached from PM, whereas the ouabain-sensitive Na+, K+-ATPase activity was preserved in the PM fragments. These observations suggest that the thyroid I- translocator consists of a protein component that is bound to PM at a site separate from Na+,K+-ATPase.