Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry.

Growth retardation as well as the development of Cushingoid features in adrenally insufficient patients treated with the currently accepted replacement dose of cortisol (33-41 mumol/day.m2; 12-15 mg/m2.day) prompted us to reevaluate the cortisol production rate (FPR) in normal subjects and patients with Cushing's syndrome, using a recently developed thermospray liquid chromatography-mass spectrometry method. The stable isotope [9,12,12-2H3]cortisol was infused continuously for 31 h at about 5% of the anticipated FPR. Blood samples were obtained at 20-min intervals for 24 h, spun, and pooled in 4-h groups. Tracer dilution in plasma was determined by liquid chromatography/mass spectrometry. The method was validated with controlled infusions in 6 patients with adrenal insufficiency. Results from 12 normal volunteers revealed a FPR of 27.3 +/- 7.5 mumol/day (9.9 +/- 2.7 mg/day) or 15.7 mumol/day.m2; 5.7 mg/m2. day). A previously unreported circadian variation in FPR was observed. Patients with Cushing's syndrome demonstrated unequivocal elevation of FPR and cortisol concentration correlated during each sample period in normal volunteers, indicating that cortisol secretion, rather than metabolism, is mainly responsible for changes in plasma cortisol. Our data suggest that the FPR in normal subjects may be lower than previously believed.

Cortisol production rate in childhood and adolescence.

We studied the daily cortisol production rate in 33 normal children and adolescents, using a stable isotope-dilution technique employing high-performance liquid chromatography-mass spectrometry. Two indwelling intravenous catheters were inserted and tracer 9,12,12-2H3-cortisol (deuterated cortisol) was infused continuously for 30 hours. After 6 hours of tracer infusion to allow for equilibration, blood was obtained every 20 minutes for 24 hours. The mean (+/- SD) cortisol production rate was 9.5 +/- 2.5 mg/day (6.8 +/- 1.9 mg/m2/day). Cortisol production rate did not vary with sex or pubertal stage. These results suggest that the cortisol production rate in children and adolescents is significantly lower than previously estimated.

The changing pattern of whole body protein metabolism in aging humans.

Dynamic aspects of whole body protein (nitrogen) metabolism were explored in healthy young adults and elderly men and women. Measurements were made of the rate of whole body protein breakdown, with the aid of 15N-glycine, and the rate of muscle protein breakdown, as estimated from urinary N tau-methylhistidine excretion. The results also were evaluated in relation to obligatory (endogenous) urinary nitrogen losses, previously determined in this laboratory for the two age groups. Rates of whole body and muscle protein breakdown, per unit body weight, were lower in elderly subjects than in young adults. Muscle accounted for a mean of 27% of whole body protein breakdown in young adults and 20% or less (p less than 0.01) in elderly subjects. Daily obligatory N loss was positively correlated (p less than 0.01) with whole body protein breakdown. It was calculated that muscle contributed less to the obligatory N output in elderly subjects than in young adults. These results indicate a change in the distribution of whole body protein metabolism during aging in human subjects, with muscle making a lower contribution to total body protein metabolism in elderly subjects compared with young adults.

Failure of yellow fever immunization to produce a catabolic response in individuals fully adapted to a protein-sparing modified fast.

In previous studies, patients consuming a protein-sparing modified fast (PSMF) did not develop the expected increase in nitrogen excretion following incidental infectious illness. To assess the catabolic response with a controlled infection in such patients, 17-D yellow fever vaccine was administered to four young obese adults after 3 weeks of this hypocaloric regimen (PSMF), essentially carbohydrate-free and providing 1.5 g protein/kg ideal body weight. Average daily nitrogen excretion from the third week of the PSMF was compared to values from the week following immunization. Contrary to the experience with malnourished children being nutritionally rehabilitated or young adults fed an adequate calorie, low (0.1 g/kg body weight) protein diet, neither urinary nitrogen excretion nor nitrogen balance was significantly affected in the study group. In three of the four subjects in the group, average nitrogen balance was positive in the week pre-and post-yellow fever immunization. In individuals fully adapted to a PSMF the metabolic consequences of mild infection on nitrogen metabolism were reduced. This may be because the usual catabolic hormones, glucocorticoid and glucagon, which are elicited by infection fail to increase nitrogen excretion in fasting or whenever dietary carbohydrate is excluded.