Biochemical studies were performed on the thyroid of a typical case of Pendred's syndrome who underwent total thyroidectomy. The patient, a euthyroid 14 year old female, presented congenital nerve deafness, goitre and impairment of thyroidal iodine organification. Thyroid peroxidase (TPO) activity was quantitatively normal. Using crude preparations, enzyme activity ranged from 176\p=n-\366 nmoles of I \ m= -\ \ x = r e q -\ incorporated (inc.) to tyrosine/g of tissue. Normal values are 220\p=n-\410 nmoles I\m=-\inc./g. Digitonin pseudosolubilized TPO, assayed by the tyrosine-iodinase method, showed 44.9 nmoles I\m=-\ inc./mg of protein for the Pendred's tissue, and 44.5 nmoles I\m=-\ inc./mg for the control glands. Soluble TPO was utilized for enzyme-kinetic studies. The Km for H2O2, obtained in the triiodide assay with iodide as hydrogen donor, was in the same order of magnitude for both Pendred's and control thyroids, being 3 \ m=x\ 10\m=-\4 m and 3.5 \ m=x\10\m=-\4 m, respectively. In the guaiacol assay, the Pendred's Km value of 4 \ m=x\10\m=-\4 m was also normal for H2O2. Pre-incubation of enzyme preparations with 5 \m=x\10\m=-\5m haematin did not stimulate TPO activity. Thyroidal NADPH-cytochrome c reductase and monoamine oxidase activities were normal. A low concentration, 37 mg/g, of a qualitatively normal thyroglobulin was found in Pendred's goitre. The iodine content of thyroglobulin was 0.19 %.

The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater Vss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the Cmax was 20 times lower than the C0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t1/2 beta ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the Vss and WBR were significantly correlated with serum alkaline phosphatase levels and the Vss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t1/2 beta after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher Vss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.

Eighteen nodules from thirteen patients with non-toxic nodular goitre were studied. The nodules were classified, according to the 131I scintiscanner, into »cold« and »warm« types. The histological diagnosis of all the glands was multinodular colloid goitre. An enzymatic system with iodide-peroxidase activity was prepared from nodular tissue obtained by surgical thyroidectomy. The enzymatic activity was determined by spectrophotometry at 287.5 nm by measuring the formation of triiodide ion. The group of »cold« nodules showed an average of 333 units of enzymatic activity and the »warm« nodules 940 units. The significance of the correlation between the capacity for iodide-uptake, the iodide-peroxidase activity and the involution of the metabolic steps in the nodular goitre is discussed.

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To change the stretch on cardiopulmonary mechanoreceptors, large shifts of blood in the capacity space were elicited by tilting and by exerting positive lower body pressure in the tilted position. Twelve volunteers underwent invasive hemodynamic studies and in 10 other subjects cardiac size was determined by radionuclide cardiography. In all 22 subjects tilting caused the expected increase of renin, which was abolished by lower body compression. Decompression caused renin to increase again. Right atrial pressure in invasive studies and end-systolic and end-diastolic counts in noninvasive studies showed a significant and strong negative correlation with renin and norepinephrine levels. Thus, the degree of stretch of the cardiopulmonary mechanoreceptors is a major determinant of reflex regulation of renin release in humans.