Observations on the Discharge of Radio-Iodine From the Thyroid Glands of Mice Injected With Human Sera

Abstract

Using Mckenzie's [1958b] modification of Adams & Purves's [1955] method for bioassay of thyrotrophin, which depends on the release into the circulating blood of radio-iodine from thyroid glands of mice, an attempt was made to measure thyrotrophin in human serum. Two types of response were encountered. The first, characteristic of hypothyroidism, resulted in a peak increase in blood radioactivity 2 hr after injection and resembles the response to standard thyrotrophin preparations. The second response, characteristic of hyperthyroidism, was delayed and the blood radioactivity did not reach a peak until 12 hr after the serum injection. The incidence of the two types of response has been investigated and several additional differences between the delayed response and the response to thyrotrophin extracted from pituitary tissue have been established.In 1955 Adams & Purves described a method for the assay of thyrotrophin by measurement of the circulating radioactivity in guinea-pigs injected with 131I and subsequently treated with thyroxine. By substituting mice for guinea-pigs, McKenzie improved the sensitivity of the method [McKenzie, 19586]. After the intravenous injection of standard solutions of thyrotrophin there was a prompt increase in blood radioactivity, which reached a peak after 2-3 hr and declined thereafter.With both methods it has been possible to demonstrate thyrotrophin-like effects following the injection of untreated serum from some patients with hypothyroidism [Adams, 1958;McKenzie, 19586], and by using a concentrated preparation of y-globulin McKenzie [19586] has obtained an estimate of the level of thyrotrophin in normal human serum.However, when attempts were made to measure the thyrotrophin content of serum from patients with hyperthyroidism, it was found that the response of the assay animals differed strikingly from that elicited either by standard preparations of thyrotrophin or serum from hypothyroid patients. With serum from hyperthyroid patients little effect was apparent by 3 hr, but there was a delayed increase in cir¬ culating radioactivity, which did not reach a maximum until 16 hr after the injection in guinea-pigs [Adams, 1958] or 12 hr in mice [McKenzie, 1958 ]. This phenomenon has been attributed to the presence of an abnormal thyroid-stimulating hormone in the serum of some patients with thyrotoxicosis [Adams, 1958].In the observations reported here the response produced by injection of serum * Present address :

Radioimmunoassay of Human Plasma Thyrotropin*

“…Using anti-HTSH serum, Adams, Kennedy, Purves, and Sirett (5) were unable to block the biological activity of LATS. More recent immunological (31) as well as a number of chromatographic, electrophoretic, and biological studies (20,(32)(33)(34) Plasma from hypothyroid patients and human pituitary extracts produced dose responses identical to that of the purified HTSH preparation. No HTSH was detectable in plasma from various animals, in plasma from hypopituitary patients, in most patients receiving exogenous thyroid therapy, or in bovine or ovine pituitary TSH preparations.…”

Pathogenesis of the Hyperthyroidism of Graves's Disease

“…Adams, 1965). It is also known that dextran solutions may show activity in this assay (Munro, 1964 (Munro, 1959) is probably another instance. The so-called " short-acting abnormal thyroid-stimulator " (S.A.T.S.)…”

“…(Adams, 1961), following the demonstration that it was active in hypophysectomized mice (and therefore did not act by stimulating T.S.H. secretion from the assay animal's pituitary) (Munro, 1959 ; Adams, Purves, and Sirett, 1961) and that it had a half-life of about seven and a half hours after injection into the circulating blood of the rat, compared with 10 to 20 minutes for T.S.H. (McKenzie, 1959;Adams, 1960 …”

“…levels tend to be reduced by prolonged administration of corticosteroids in high dosage (Kriss et al, 1964 Green, Snyder, andSQlomon, 1963). The tendency for hyperthyroidism to remit during pregnancy (Munro, 1964) (Roitt and Doniach, 1960). The titre of thyroid antibodies rises transiently after l"1I therapy, which apparently intensifies the antigenic stimulus (Irvine, 1964).…”

The aetiology and pathogenesis of hyperthyroidism

“…A prolonged response can also be obtained by I I repeated administration of TSH in divided doses (Hoffman et al, 1967), suggesting a similar mode of action of the two principles on the thyroid gland. When sera known to contain TSH and the abnormal activity are mixed the effect of the two agents is additive (Adams, 1958;Munro, 1959). The thyroid-stimulating activity of thyrotoxic plasma was also evident in the hypophysectomized mouse indicating that it acts directly on the thyroid.…”