J.W.K. Robertson

Concentration of 35S-propylthiouracil by the thyroid gland and its relationship to anion trapping mechanism

Abstract Propylthiouracil is concentrated by the thyroid gland in rats and man. Four 35 S compounds were demonstrated in the rat and human thyroid by thin-layer chromatography: sulphate, intact propylthiouracil, an unknown metabolite X and origin 35 S activity which is protein bound. Unbound 35 S compounds in plasma include propylthiouracil, the glucuronide conjugate of PTU, sulphate, and X. The thyroid concentration rather than the plasma level of propylthiouracil determines the duration of inhibition of organic binding of iodine in the thyroid. The effect of perchlorate and iodide on the thyroid concentrating mechanism for 35 S-propylthiouracil and 125 I-iodide was studied. The level of perchlorate and iodide which almost completely blocked the concentration of 125 I-iodide also partially reduced the concentration of 35 S-propylthiouracil. Iodide but not perchlorate decreased the rate of metabolism of 35 S-propylthiouracil in the thyroid gland.

Simultaneous Measurement of Total Exchangeable Potassium and Sodium Using 43K and 24Na

The simultaneous measurement of total minations (Ke at 44 hr 1.93%; Na. at exchangeable potassium and total ex- 24 hr 1.77O/o) appear comparable to or changeable sodium is described using better than the results of previous stud43K and 24Na in 67 patients. Smaller ies. The whole-body radiation dose to doses of radioisotope were used than the patient was estimated at 17 mrad. previously reported, but despite this a Eight patients had independent meas44-hr mixing period was achieved for urements of body potassium (40K), and potassium. The coefficients of variation these were in close agreement with the for duplicate estimations of radioactiv- Ke value. It is felt that 43K should reity (potassium. 2.5%, sodium 1.51%) place 42K for the measurement of total or for exchangeable electrolyte deter- exchangeable potassium in man. S IMULTANEOUS MEASUREMENTS of total exchangeable potassium (Ke) and total exchangeable sodium (Na@) are often required in the assessment of metabolic disease. Until now the isotopes 22Na (Tlh 2.6 yr), 24Na (TG 15 hr) and 42K (TIA 12.4 hr) have been used,le8 but recentIy the use in man of 43K (T4a 22 hr) has been described.9 43K with gamma emission between 0.37 MeV and 0.61 MeV can readily be distinguished from 24Na by gamma counting. The technical procedures are simple, and, despite the longer half-life, the lower beta and gamma ray energies of 43K result in only 70% of the whole body radiation dose per microcurie to the patient when compared with 42K. A technique for simultaneously measuring exchangeable body potassium and sodium using smaller doses of 43K and 24Na than described by previous workers is reported.

Quantitative aspects of pertechnetate concentration in human parotid and submandibular salivary glands

Quantitative uptakes of 99Tcm-pertechnetate by the salivary glands have been measured in 36 subjects and normal values established. While uptake over the parotid gland increased with time, parotid uptakes were higher at all time intervals than uptakes over the submandibular glands. The uptake over the submandibulars also increased with time. There was no significant difference between resting uptakes of right and left glands, a significant difference would therefore suggest the presence of pathology. Values over the parotid gland are greater under resting conditions than following stimulation, but no such difference was noted for submandibular glands. However, with stimulated glands it was also shown that there was no significant difference between the right and left parotid, or rignt and left submandibular uptakes. The clinical relevance of these findings is discussed.

Quantitative studies of the inhibitory effect of perchlorate on the concentration of 36ClO4−125I− and 99mTcO4− in salivary glands of male and female mice

[36Cl]-Perchlorate, [125I]-iodide and [99mTc]-pertechnetate were concentrated in the mouse submandibular salivary gland in the order 36ClO4− = 99mTcO4− >125I−. Gland plasma (GP) concentration ratios for 36ClO4− and 99mTcO4− rose to a maximum of 12 compared to a value of five for 125I−. In the case of all the anions studied, a significantly higher concentration was observed in male compared to female mice. This anion concentration difference between the sexes was of the same order for 36ClO4− and 99mTcO4− and was smaller in the case of 125I−. Results suggest that 36ClO4− is concentrated in the duct cells of the salivary gland. The serum perchlorate levels required to decrease the (GP) ratio to 1 varied for the different anions and was in the order 99mTcO4− >36ClO4− >125I−. The concentration of perchlorate required to inhibit the concentrating mechanisms for the three anions was greater in males than females. The lowest dose of ClO4− used (0.28 μ-equiv./kg) was such that it did not inhibit 125I−or 99mTcO4− uptake in either sex. With a dose of 1.43 μ-equiv./kg, the ClO4− concentrating mechanisms for 125I− and 99mTcO4− were inhibited in the female but not in the male.

Sex differences in human parotid salivary secretion of iodide, pertechnetate and bromide.

Abstract Parotid salivary flow rates were studied using a variety of stimuli in convalescent patients after injection of a solution containing 132I, 99mTcO4− and 82Br. Lemon juice and salt produced significantly higher flow rates in men than in women. However, for any given flow rate there was no significant difference between the sexes in the saliva to plasma ( S P ) ratio produced by any of the anions. The inverse relation between the S P ratio of each of the anions and salivary flow rate was confirmed.

The concentration of iodide and pertechnetate in the submandibular salivary gland of the mouse.

Abstract The concentration of 131 I-iodide and 99m Tc-pertechnetate was measured in mouse submandibular salivary glands and plasma at time intervals up to 300 min after simultaneous administration of the two isotopes. The T S ratio for iodide rose to a value of 7 and for pertechnetate to a value of 16 at 300 min. From 60 min the T S ratio for iodide was approximately half the value for pertechnetate. Previous studies in human parotid saliva have suggested that the T S ratio for iodide is significantly greater than the T S ratio for pertechnetate. The relative capacity for concentration of these ions may, therefore, vary from species to species.

Self-limiting episodes of recurrent thyrotoxicosis

Summary 5 patients with recurrent thyrotoxicosis experienced a remission without anti-thyroid therapy. The initial episode of thyrotoxicosis was treated with carbimazole, and after completing treatment the patients remained in remission for periods of up to 16 months. At the time of recurrence clinical features of thyrotoxicosis were accompanied by elevation of thyroid radioiodine uptake, protein-bound iodine, and free-thyroxine index. Subsequent clinical improvement was paralleled by a return of values to normal. Conventional treatment of these relapses of thyrotoxicosis by radioidine therapy or subtotal thyroidectomy might not have conferred any advantage on these patients.

Simultaneous Quantitative Measurement of 131I-Iodine and 99mTc-Pertechnetate Uptake by Human Salivary Glands Using Scintiscanning with Validation by Direct Estimation in Biopsy Samples

Abstract. 131I‐iodide and 99Tc‐pertechnetate concentration in human salivary glands has been measured simultaneously in vivo by quantitative scintiscanning in 7 thyrotoxic subjects. The mid scan times were 5, 12 and 20 min. and the gland to plasma ratio (G/P) of 131I rose to 4.03±0.82 (s.e.) in the parotid and 10.7 ±3.1 (s.e.) in the submandibular glands. Corresponding values for G/P 99mTcO4‐were 2.70 ±0.34 in the parotid and 5.3 ± 1.2 in the submandibular glands. Values obtained at parotidectomy 1 h after intravenous administration of a mixture containing 125I‐ and 99mTcO4‐ to 6 patients were 4.13 ± 0.85 for G/P 125I‐ and 2.50 ± 0.62 for G/P99mTcO4‐. G/P131I‐ (or G/P125I‐) and G/P 99mTeO4‐, derived by both methods, were significantly correlated in parotid and submandibular glands. There was a significant correlation between G/P 131I‐/G/P 99mTcO4‐ in the parotid glands and G/P131I‐/G/P99mTcO4‐ in the submandibular glands. ‐It is concluded that 1. salivary gland values of 131I‐ and 99mTcO4,‐as measured by scintiscanning are very close to values obtained by direct counting of excised human salivary gland tissue and 2. that the secretion processes in both glands are physiologically related.

131I Concentration in Submandibular Salivary Glands of Rats and Mice

In a recent report Esposito (J Dental Res 49: 459, 1970) studied the time course of iodide concentration in the submaxillary gland; he used the rat as his experimental animal. Although iodide is concentrated in salivary glands of humans and other species (B. COHEN and N. B. MYANT, J Physiol 145:595, 1959 and R. McG. HARDEN and W. D. ALEXANDER, Clin Sci 33:425, 1967), previous studies have shown that iodide is not concentrated in submandibular saliva (J Physiol 145:595, 1959) or in the submandibular salivary gland, in vivo or in vitro (K. BROWN-GRANT, J Physiol 165:519, 1963), in the rat. In the latter study the glandblood ratio was less than one, and was not affected by large doses of thiocyanate. Espositos conclusion that there was an affinity of the submaxillary glands for 131I was not confirmed by his published data, because blood radioiodine or gland-blood radioiodine ratios mere not reported. It seemed likely that the time course during which iodide appears in the salivary glands might be different in animals such as the rat, which does not concentrate iodide, and the mouse in which iodide is concentrated to several times the plasma level (K. W. STEPHEN, R. McG. HARDEN, and J. W. K. ROBERTSON, Arch Oral Biol 15:425, 1970). Therefore, we studied the time course of iodide concentration in the submandibular salivary glands of the two species. Seventy-two male albino mice (AS 1 strain) that weighed 25 + 1 gm each were studied. Two gic 131I in 0.2 ml saline solution was injected intraperitoneally. The activity in the submandibular glands and in the blood of four mice was studied at each of the following time intervals: 1, 2, 3, 4, 5, 7.5, 10, 15, 20, 25, 30, 40, 50, 60, 75, 90, 120, and 180 minutes after isotope injections as described previously (Arch Oral Biol 15:425, 1970). Nine male SpragueDawley rats weighing 250 gm each were studied in the same way. Rats were killed by exsanguination at 1, 5, 10, 20, 30, 40, 60, 120, and 180