Sheep have been used to study the effect of dietary iodine deficiency on the development of the fetal brain. Severe iodine deficiency caused reduction in fetal brain and body weights and in brain DNA and protein from 70 days gestation to parturition. The lowered brain weight and brain DNA at 70 days gestation indicates a reduced number of cells, probably due to slower neuroblast multiplication which normally occurs from 40-80 days in the sheep, and the reduction in DNA and protein after 80 days implies that the development of neuroglia could be slowed also in iodine deficiency. Morphological changes were observed in both the cerebral hemispheres and the cerebellum. In the cerebral hemispheres of the iodine-deficient fetuses an increased density of neurons was apparent histologically in the motor cortex and visual cortex and in the CA1 and CA4 areas of the hippocampus in comparison with controls. In the cerebellum there was delayed migration of cells from the external granular layer to the internal granular layer and increased density of Purkinje cells in the iodine-deficient fetal brains. In addition, the molecular area was increased and the medullary area reduced in comparison with controls. These change are indicative of delayed brain maturation. Evidence of fetal hypothyroidism was provided by low fetal thyroid iodine and plasma T4 values, thyroid hyperplasia from 70 days gestation, significant reduction in body weight at the same time as the brain retardation, and absence of wool growth and delayed skeletal maturation near parturition. It is apparent from the biochemical and histological changes observed during iodine deficiency that iodine is an essential element for normal fetal brain and physical development in the sheep.
The ingestion by normal subjects of 3 g of sodium iopodate, which is widely used in routine oral cholecystography, resulted in significant decreases of serum total and free T3 to a nadir on day 4 which averaged 43% and 40%, respectively, below initial mean values. Total and free rT3 increased markedly to a peak on day 3, 244% and 189%, respectively, above initial mean values. Total and free Ti and free T4 index rose to a maximum on day 4, but these changes were not statistically significant. A marked TSH increase was also seen, most evident on day 3. All these changes reverted to baseline values by day 14 at a time when serum total iodide was still markedly elevated. It is concluded that the changes observed after iopodate were not due to alterations in serum binding proteins nor to an effect on thyroid gland by the large iodine component of iopodate, but were consistent with an effect on the peripheral metabolism of T4. Difficulty in ipterpreting routine thyroid function tests may occur for up to 14 days after oral cholecystography with iopodate. Sodium iopodate is a contrast medium commonly used in oral cholecystography. Its chemical struc¬ ture bears some similarity to that of thyroxine (T4) and 61.4% of its weight consists of iodine. Wu et al. (1978) observed the effects of iopodate ingestion for a week and showed that serum 3, 5, 3' triiodothyronine (T3) decreased, 3, 3', 5' triiodothyronine (rT3) increased and T4 increased in euthyroid subjects. Similar changes were observed in thyrotoxic patients excepting that serum T4 decreased. They concluded that iopodate alters peripheral metabolism of T4 and, in thyrotoxicosis, it may decrease thyroid activity also.Because of its widespread use in clinical practice iopodate may commonly complicate the interpreta¬ tion of routine thyroid function tests. We therefore decided to document the magnitude and duration of such interference by observing the effects of oral iopodate on routine thyroid function tests. We also studied the effects on the serum concentrations of total and free rT3, free T3, free T4, thyroid stimu¬ lating hormone (TSH) and total iodide to help elucidate the mechanism of the interference. Subjects and MethodsSix healthy adult male volunteer subjects were studied whose average age was 25 years. Sodium iopodate was given in 3 separate 1 g oral doses between 09.00 and 12.00 h. Similar studies were conducted on two other healthy volunteers given an equivalent oral dose of iodine in the form of potassium iodide. Blood was sampled by venepuncture at 09.00 h on each day of observation namely 10 and 6 days before iopodate, on the day of taking iopodate and on days 1, 3, 4, 7, 14 and 21 after the doses. Samples were taken with minimal venostasis after the subjects had been sitting for 5 min. Serum was stored in aliquots and analyzed soon after the last sample was collected. All samples from each subject were analyzed in the same batch.Concentrations of total T4, total T3, rT» and the TSH were determined by specific radioimmunoassay (RIA) using second anti...
Elective surgery was used as a model of severe non-thyroidal illness (SNTI) to study the inter-relation between changes in serum thyroid hormones, thyroid stimulating hormone (TSH), cortisol, and interleukin 6 concentrations. The study was designed to determine whether the expected interleukin 6 increases after surgery are the cause of decreased serum tri-iodothyronine (T,) Total T, free T, free T4, and TSH concentrations were measured using an "Amerlite" (Kodal Clinical Diagnostics, Amersham, UK) automated enzyme immunoassay (luminescence signal), the lower limit of detection (LLD) for TSH being 0 03 mU/l. Serum interleukin 6 concentrations were measured using an ELISA ("Biotrak"; Kodak) with a LLD of 1 pg/ml and coefficients of variation of 3-5% (intra-assay) and 7 0% (interassay). Cortisol concentrations were measured using a ("Amerlex"; Kodak) radioimmunoassay.Results
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