1. Investigación

Introduction. Renal function and thyroid metabolism are tightly related. However, evidence about subclinical hypothyroidism prevalence in patients with chronic kidney disease and its related factors is scarce. Objectives. Our aim is to analyze subclinical hypothyroidism prevalence and its related factors in patients with advanced chronic kidney disease. Materials and methods. Nondialysis-dependent patients with chronic kidney disease at stages 3 to 5 were included. Other inclusion criteria were age above 18 years and clinical stability. Patients with diagnosed thyroid illnesses were excluded. Subclinical hypothyroidism was de ned as thyroid stimulating hormone (TSH) > 5.3 mU/L, with free thyroxine 4 (FT4) between 0.54 and 1.24 ng/dl. Filiation data, comorbidities, and routine blood and urine test results were registered. Results. A total of 299 patients were included. Of them, 184 (61.5%) were men. The mean age was 71 ± 13 years old. The mean glomerular fltration rate (CKD-EPI) was 22 ± 9 ml/min/ 1.73m2. According to chronic kidney disease stages, global distribution of patients was as follows: Stage 3, 67 patients (22.4%); Stage 4, 155 patients (51.8%); and Stage 5, 77 patients (25.8%). We found subclinical hypothyroidism in 54 (18.1%) patients. According to chronic kidney disease stages, distribution of affected patients was as follows: Stage 3, 9 patients (13%); Stage 4, 25 patients (16.1%); and Stage 5, 20 patients (26%). Di¤erences among stages were statistically signifcant. By univariate analysis, factors related with subclinical hypothyroidism were as follows: age RR 1.048 (95% CI 1.019–1.078; p = 0.001), hypertension RR 2.705 (95% CI 1.026–7.130; p = 0.04), glomerular fltration rate RR 0.962 (95% CI 0.929–0.996; p = 0.03), and proteinuria higher than 1 gram/day RR 2.387 (95% CI 1.303–4.374; p = 0.005). By multivariate analysis adjusted by age, hypertension, glomerular fltration rate, proteinuria, diabetes, and cardiovascular disease history, only age RR 1.016 (95% CI 1.009–1.028; p = 0.04) and glomerular fltration rate RR 0.963 (95% CI 0.930–0.997; p = 0.03) preserved their independent association with subclinical hypothyroidism. Conclusions. Subclinical hypothyroidism prevalence in patients with chronic kidney disease is high and increases with renal disease severity. Factors independently related to subclinical hypothyroidism are age and glomerular fltration rate.

1.8 or 25 µg of L-thyroxine/100 g body wt. were compared with intact controls (C). The appearance of radioacitvity in fatty acids 30 min after the i.p. injection•of (3-14C)pyruvate was reduced in adipose tissue and enhanced in liver of T+25, being no differences between the other groups and C. ( 14C)- Fatty acids are reduced with 3 h of fasting only in the adipose tissue of T+ 1.8 and C, while 24 h produces a reduction in liver in the T+ 1.8, T+25 and C, and in adipose tissue in the T+l.8 and C animals. The highest percentage of radioactivity was observed in the liver glyceride glycerol fraction, being greater in T+25 than in the other groups. Fasting produces an increment in the ( 14C)-glyceride glycerol fraction. being significant only in the hypothyroid animals in both liver and adipose tissue. The most sensitive parameter to fasting was the formation of ( 14C)-non-saponifiable lipid in both the C and T+ 1.8 animals, while it does not change in T+0 or T+0.I, but is enhanced within 24 h in the adipose tissue of T + 25. It is proposed that most of the observed changes are due to the other endocrine disfunction s which appear in hypo- and hyperthyroidism, as the in vivo results do not comply with in vitro effects of thyroxine on lipogenesis of others.

To determine adipose tissue cellularity in hypo- and hyperthyroidism, male rats were thyroidectomized after weaning (T) and injected daily with either 0, 0.1, 1. 8, or 25 µg of L-thyroxine/100 g body weight for 40 days. They were compared with intact controls (C). Both epididymal fat-pad weight and adipocyte diameter were reduced in T+0, T+0.1 and T+25 animals. When corrected per unit of body weight, the diameters of adipocytes from T+0 and T+0. l animals were larger than in the other groups. Those same animals have reduced absolute adipocyte number but not when corrected per unit of body weight. The fat-pad protein concentration varied conversely with the fat cell diameter. These findings indicate that thyroid hormone deficiency reduces thf proliferation of fat cells in parallel with body growth while hyperthyroidism causes reduction in the size, but not the number, of fat cells which corresponds to its depletion of fat storage.

1) Thirty days after surgical thyroidectomy, one group of rats were made diabetic by treatment with streptozotocin and were studied for the next 14 days. These diabetic thyroidectomized animals were similar in body weight to their thyroidectomized controls but had higher plasma concentrations of most amino acids. 2) Treatment with 0.5, 1.0 or 2.0 µg of L-thyroxine/100 g body wt for 7 days prior to sacrifice produced no changes in either parameter in the diabetic thyroidectomized animals. On the contrary, in thyroidectomized controls, the Lthyroxine treatment was followed by a dose-dependent increment in body weight. In these animals, the administration of 0.5 µg of L-thyroxine per day was associated with a marked rise in the plasma level of most amino acids, while only basic amino acid levels increased with 1.0 µg, and levels decreased with 2.0 µg. 3) In the diabetic thyroidectomized rats treated with insulin for the last 7 days before sacrifice, body weight gain and the biphasic change of plasma amino acid levels were restored. 4) It is proposed that treatment of thyroidectomized controls with small doses of L-thyroxine accelerate protein breakdown accompanied by minor changes in amino acid utilization, while this latter effect increases with higher doses of the hormone. 5) Present results demonstrate that a certain amount of circulating insulin is required to obtain the response to exogenous thyroxine in diabetic thyroidectomized animals. Results are discussed in terms of the role of interhormone synergism as it affects normal sensitivity of the different hormones.

Plasma amino acid concentrations, together with other metabolic parameters were determined in thyroidectomized rats treated with daily injections of sal ins (hypothyroid), and 250 ,ug/kg L-T4 {hypothyroid). Data were compared with sham-operated controls. TherP. is a genera! incre'!SE> in plasma amino acid concentrations in hyperthyroidism, a limited in· crease only in several amino acid r.oncentrations in hypothyroid rats as compared with controls, and a considerable difference between the plasma aminograms of both groups. Amino acid homeostasis seems to be subject to greater modification in hyperthyroidism than in hypothyroidism.

1) Thyoridectomized rats were fed with a low iodine diet, injected daily with 0, 0.1, 1.8 or 25 µg of L-thyroxine/100 g body wt., and compared with intact controls. 2) Plasma protein-bound iodine was decreased in the rats given the 0 and 0.1 µg doses, unchanged in those given the 1.8 µg doses, unchanged in those given the 1.8 µg dose increased in those given the 25 µg one. 3) The liver content of DNA-P, phospholipid-P, proteins and fatty acids was decreased in the rats that did not receive thyr.oxine, practically recuperated in those receiving 0.1 µg and normal in those given 1.8 or 25 µg of thyroxine. 4) 3 h of starvation produced a reduction in the liver content of total fatty acids that disappeared after 24 h. 5) When fod, liver glycogen concentration was low in the rats given 25 µg of thyroxine. 6) With starvation, the fall in liver glycogen and blood glucose, and the rise in liver acetylCoA and citrate and blood glycerol concentrations were faster in the thyroidectomized rats that did not receive thyroxine than in the other groups. 7) The rise in plasma free fatty acid and blood ketone bodies concentrations were similar in all the groups, the greater level of the first parameter being observed after 6 h of starvation in the rats given 25 µg of thyroxine and in the second one after 24 h in the rats given either 0.1, 1.8 or 25 µg of thyroxine. 8) The rapid decrease in the availability of carbohydrate stores with starvation in the thyroidcctomized rats could be responsible for their fast call for lipid utilization. The slower response to fasting in the hyperthyroid animals is probably a consequence of their reduced amount of endogenous substrates to be mobilized.