T4-, T3- and reverse-T3 concentrations were measured in the sera of 365 subjects beyond the age of 65 in order to evaluate if the decrease of serum T3 frequently observed in old age can be attributed to old age per se or to concomitant nonthyroidal disease. The results obtained from a carefully selected healthy group of elderly people show that 1) total and free T3 levels are lower in senescence but well within the range for euthyroidism in younger healty controls;2) the decrease of serum T3 is more pronounced and occurs earlier in healthy old males than in females, so that for subjects over the age of 75, the upper limit for euthyroidism has to be adjusted by 10% in women and by 20% in men; and 3) there is no low T3 syndrome characterized by decreased serum T3 and increased serum reverse T3, solely due to old age. Turnover kinetics have shown the daily production of T4 and T3 in old age to decrease by 20 micrograms and 10 micrograms, respectively, and an increased T3 metabolic clearance not to account for the reduction of serum T3 concentrations. Combined stimulation tests with TSH and TRH showed that the functional reserve of the thyroid gland to produce T3 is maintained in old age. The first step in the sequence of events may be seen in an impairment of TSH secretion leading to an adaptation of the amount of thyroid hormones to a reduced mass of metabolically active body tissue in old age.
In severely ill patients of an intensive care unit overt peripheral thyroid hormone deficiency was noted in 22 of 33 subjects. The TRH-test was performed in 7 of these 22 patients and was negative in all. Thus, the laboratory data suggest secondary hypothyroidism. The laboratory diagnosis, however, could not be supported by clinical signs probably due to the short period of observation and to the strongly elevated body temperature of the respective patients. The pathogenetic mechanism is not clear. However, all patients developing secondary hypothyroidism were treated with dopamine and/or glucocorticoids, compounds known to inhibit pituitary TSH release and most of the patients had septic fever. A persistently "hypothyroid state" (total T4: 23 +/- 15 nmol/l, free T4: 6.1 +/- 3.2 pmol/l, total T3: 0.28 +/- 0.22 nmol/l, S.D.) is associated with a very poor prognosis. In view of the negative effects of a hypothyroid state, substitution of thyroid hormones must be considered in this situation.
Initial velocities of energy-dependent Ca2+ uptake in cardiac mitochondria were measured with the ethyleneglycol bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid/ruthenium red quenching technique. Accurate concentrations of free Ca2+ between 1 and 15 pM were generated with ATP as a Ca2+ buffer system. Using the method of iterative approximation, the accurate value of the initial velocity of ATP-driven 45Ca uptake, and the time (t0.5) for half-maximal uptake can be calculated.The rate of initial Ca2+ uptake increased in response to the rising free Ca2+ concentrations in the medium (in the presence of 0.6-5.0 mM ATP). A maximal rate was obtained between 10 and 15 pM of free Ca2+. For different ATP concentrations (0.6-5.0 mM), the half-maximal rate of CaZ+ transport (K,,,) was observed between 4.1 and 7.4 pM Ca2+ (with a mean K m of 5.6 f 0.6 pM Ca2+; n = 5). Hill plots of the data yield straight lines with an average slope n of 1.93 f 0.29, indicating the existence of two binding sites for Ca2+ in the transmembrane transport system. Keeping the free Ca" concentration on a constant level (6 pM), the rate of initial Ca2+ uptake also increased continually with rising ATP concentrations (maximum velocity u = 7
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