Growth potential among people with Type 1 diabetes and subclinical hypothyroidism may be significantly reduced. Growth was evaluated in 25 children with diabetes who had thyromegaly and elevated thyrotrophin (TSH) levels. All patients appeared clinically euthyroid except for four with short stature. Basal growth rate was significantly lower (p less than 0.005) in Group 1 (TSH greater than 50 mU l-1) and Group 2 (TSH level 10.1-50 mU l-1) than in patients with TSH levels between 5 and 10 mU l-1 (Group 3) or control diabetic children. Serum thyroxine (T4) levels were significantly lower (p less than 0.05) in Group 1 than in Groups 2 or 3. Significant improvement in growth velocity after thyroxine treatment was observed in Group 1 patients compared with those in Groups 2 or 3 (p less than 0.05). More prepubertal test children demonstrated improved growth after beginning thyroxine compared with matched diabetic controls (p less than 0.02). Postpubertal subjects treated with thyroxine did not show significant differences in growth velocity compared with controls. Z-scores for height were not different (p greater than 0.05; ANOVA) between control and test patients for any of the groups. Early detection of subclinical hypothyroidism by thyromegaly, reduced growth velocity, and elevated TSH levels, with institution of thyroxine treatment, can improve growth in prepubertal diabetic children.

Young adult ovariectomized rats were used to investigate the pathogenesis of ovarian hormone deficiency osteopenia, uncomplicated by other forms of age-related bone loss. It was observed that the femurs of ovariectomized rats were less dense with less hydroxyproline and less calcium (Ca) and phosphorus per unit volume of bone than those of age-matched controls. Compared to animals killed at the beginning of the study to serve as baseline controls, ovariectomized rats and their age-matched controls had increased periosteal and cortical areas, but in contrast to the age-matched controls, ovariectomized rats had markedly increased medullary area and the ratio of their cortical area to periosteal area was decreased (P less than 0.02). When the changes in cross-sectional areas were expressed as percent of the baseline levels, the medullary area was increased 32% in ovariectomized rats, and only 14% in the age-matched controls; the net increase in cortical area was 17% for the controls and 11% for the ovariectomized rats and there was only 3% difference between the increases in their periosteal areas. Furthermore, ovariectomy caused a marked decrease in serum calcitonin and Ca levels but not in PTH levels. As expected, PTH administration increased serum Ca in all rats, but the rise was greater in ovariectomized calcitonin-deficient rats than in rats that were only ovariectomized or only thyroidectomized. Whereas these findings support the concept of increased sensitivity of bone to PTH in ovarian hormone deficiency osteopenia, the decrease in serum Ca in ovariectomized rats indicates that other factors may be involved as well.

No abstract

Studies were carried out on SPF F344 male rats to evaluate the effects of aging and life-prolonging food restriction, without malnutrition, on rat skeleton and circulating PTH. Six-week-old F344 rats were divided into five groups. Group 1 rats were fed ad libitum a diet that contained 21% protein. Group 2 rats were fed 60% of the mean food intake of group 1 rats from 6 weeks of age for the rest of their lives. Group 3 rats were fed 60% of the ad libitum food intake until 6 months of age and then switched to ad libitum feeding. Group 4 rats were fed ad libitum until 6 months of age, and then switched to 60% of the ad libitum food intake. Group 5 rats were fed ad libitum a diet that contained only 12.6% protein so that these animals ingested the same amount of protein per day as the group 2 rats. In group 1 animals, bone length, weight, density, and calcium content increased rapidly with age and plateaued at about 12 months of age. There was no evidence of bone loss in these animals until about 24 months of age, but by 27 months, the animals had lost appreciable amounts of bone. The circulating immunoreactive PTH levels of the animals increased with advancing age, with a marked rise at 27 months. The age-related changes in bone and serum PTH levels of rats in groups 3 and 5 were similar to those of group 1 animals, except that a terminal increase in serum PTH did not occur in group 5 rats. In the groups 2 and 4 animals which were food restricted for the longest period, bone growth and maturation were slowed down, but the animals did not experience senile bone loss or marked terminal increase in circulating PTH. The salutary effects of food restriction were, therefore, not due specifically to the restriction of protein intake or to restricting food intake only during the period of rapid growth.

Studies were carried out on specific pathogen-free rats to evaluate the effects of aging and dietary manipulation on serum and thyroid calcitonin (CT) levels. Male Fischer 344 rats were randomized at 6 weeks of age to six dietary groups and subsequently maintained on the following dietary regimens. Group 1 rats were fed ad libitum throughout life; group 2 rats were fed 60% of the ad libitum food uptake, but received the same amounts of calcium, phosphorus, and vitamin D; group 3 rats were fed as the group 2 animals until 6 months of age and from then on were fed ad libitum; group 4 rats were fed ad libitum until 6 months of age and then switched to 60% food restriction; group 5 rats were fed ad libitum on food isocaloric with that of group 1 rats, but containing only 60% of the protein. Group 6 rats were killed at 6 weeks of age to serve as baseline controls. Ten rats were killed in each of the remaining five groups 15 h postprandial at 6-month intervals. The following observations were made. Serum CT increased with age similarly in the ad libitum fed group 1 and 5 rats. Food restriction markedly inhibited the increase in serum CT, and the effect was more profound in animals whose food intake was restricted after 6 months of age (group 4) than in animals on lifelong food restriction (group 2). In rats switched from food restriction to ad libitum feeding (group 3) at 6 months of age, serum CT increased with age to levels identical with those of lifelong ad libitum fed group 1 animals. Thyroid CT showed a similar pattern of age-dependent and dietary modulated changes. In contrast, aging and dietary modulation had no appreciable effect on serum calcium levels, except at 27 months of age when the serum calcium level of group 1 animals increased dramatically from the level for 24-month-old animals. There was a weak positive correlation between serum calcium and serum CT (r = 0.627; P = 0.02) and a highly significant positive correlation between serum CT and thyroid CT (r = 0.917; P = 0.001). These findings indicate that elective and therapeutic restriction of food intake might also attenulate CT levels in humans, with potentially adverse implications for skeletal homeostasis.