J. Enrique Silva

Thyroid nodularity after childhood irradiation for lymphoid hyperplasia: a comparison of questionnaire and clinical findings

Ionizing radiation is a well-established cause of thyroid cancer and nodularity, however, important questions relating to the magnitude of the risk following low-dose medical exposures remain unresolved. To address these issues, we conducted a follow-up study of 1590 individuals treated between 1938 and 1969 with X-rays for childhood lymphoid hyperplasia (av. thyroid dose = 24 cGy) and 1499 individuals treated with surgery only. Thyroid nodularity was determined from self-administered questionnaires completed by 1195 irradiated and 1063 surgically-treated subjects and from clinical examinations of 602 irradiated and 457 non-irradiated subjects. A much higher relative risk (RR) for radiation-induced thyroid nodules was estimated from the questionnaire than from the clinical examination data, 15.8 and 2.7, respectively. (The corresponding estimates of excess RR per cGy were 64 and 7%). Analysis of the examination data revealed a strong dose-response relationship, similar excess RR/cGy for males and females, and an inverse relationship with age at exposure. Although the thyroid gland is one of the most sensitive organs to the neoplastic effects of radiation, the radiation-induced risk of thyroid nodularity reported from questionnaire studies may over-estimate the true risk.

Bioavailability of thyroid hormones from oral replacement preparations

We evaluated gastrointestinal absorption in normal subjects of T4 and T3 from synthetic T3 tablets (Cytomel, SKF), desiccated thyroid tablets (Armour), thyroglobulin tablets (Proloid, Warner-Chilcott) and synthetic L-T4 tablets (Synthroid, Flint and Levothroid, Armour). Measurements of serum T4 and T3 concentrations and free hormone indices were made at multiple times after tablet ingestion, and T3 content in tablets was measured by radioimmunoassay. The time to peak serum T3, and the 26 hr intergrated increment in serum T3, Corrected for the amount if T3 ingested, were not significantly different for 75 micrograms of synthetic T3, 6 grains of desiccated thyroid (containing 99 micrograms T3) and 5 grains of thyroglobulin (containing 90 micrograms T3), the mean integrated increment values for the biological preparations being within 12% of those for synthetic T3. The peak serum T4 concentration, the time to peak T4, and 48 hr integrated increments in serum T4 and T3 were similar after 3 mg of Synthroid and Levothroid. The mean peak serum Free T3 Index after 75 micrograms T3, 500, was much higher than the mean peak Free T3 Index after 3 mg T4, 290. The time to peak Free T3 Index was much less after 75 micrograms T3, 2 hr, than the time to peak after 3 mg T4, 2 days. These results indicate that the time course and extent of T3 absorption do not differ, whether the T3 is given as the synthetic iodothyronine or as part of the thyroid protein, thyroglobulin. This approach appears to be useful in determining bioavailability of thyroid hormones from oral preparations and to assess the possibility of thyroid hormone malabsorption.

Role of the Pituitary Iodothyronine 5’Deiodinase Activity in the Negative Feedback by Thyroid Hormone upon TSH Release

It is widely accepted that triiodothyronine (T3) accounts for nearly all of the thyromimetic potency of thyroidal secretion. The nuclear thyroid hormone receptors bind T3 with > 10-fold higher affinity than thyroxine (T4), and the intracellular concentration of T4 is not enough to occupy more than 10f of these receptors—a substantial fraction of which may actually be non-specifically bound. About a decade ago, this and the relatively rapid exchange of plasma T3 with the receptor, led to the concept that the thyroid status of the tissues was closely reflected by the plasma concentration of T3 (1).