Steroid-induced osteoporosis. Are your asthmatic patients at risk?

Asthmatic patients who rely on long-term, high-dose corticosteroid therapy are at increased risk for osteoporosis. The use of low-dose inhaled corticosteroids may be safe enough not to require special assessment of bone loss or preventive measures. However, evidence is lacking on the risks of long-term use of higher doses. Regardless of dose, all patients given long-term systemic corticosteroids should be carefully examined and, if necessary, treated for bone loss.

Glycogen concentration and regulation of synthase activity in rat liver in vivo.

The proportion of liver glycogen synthase in the active (R+I) forms is lower in the fed than in the fasted state. This has been attributed to inhibition of synthase phosphatase by the accumulated hepatic glycogen. We observed that after oral administration of glucose or galactose to fasted rats, hepatic synthase R+I activity first increased, as expected, but then decreased to a nadir significantly below the control level regardless of the maximal glycogen concentration reached. Therefore, we investigated further the relationship of hepatic synthase R+I activity and glycogen concentration in vivo in fasted rats given increasing oral glucose loads. Male rats fasted 24 h were given glucose doses of 0.1-4.0 g/kg by oral gavage (n > or = 8). Liver synthase R+I, total synthase, phosphorylase a, glucose, glycogen, glucose-6-P, and UDP glucose were measured at intervals over 20-240 min after gavage. Even the smallest glucose load elicited rapid glycogen synthesis. The maximum glycogen concentration increased linearly with the size of the glucose load, although the proportion of administered glucose accounted for by liver glycogen decreased as the glucose load increased. The proportion of synthase in the active (R+I) forms peaked at 20 min after all doses and then declined. By the time the glycogen concentration was maximal, synthase R+I activity had decreased to the control value, regardless of the glucose dose administered or the maximum glycogen concentration reached. Although the decrease in synthase R+I at the time of the glycogen peak was correlated with the increase in glycogen concentration, synthase R+I continued to decrease for another 1-2 h even though liver glycogen was stable or decreasing. The nadir reached was independent of the maximal glycogen concentration. The synthase R+I nadir also did not correlate with hepatic glucose or glucose-6-P concentrations or phosphorylase a activity. Overall, there was not a straightforward temporal or quantitative relationship between the glycogen concentration and synthase R+I activity. These data suggest a more complex mechanism than simply direct inhibition of synthase phosphatase by glycogen.

Osteoporosis in men. Is it more common than we think?

Men are most at risk for hip fracture as they grow older because of age-related loss of bone in the femur. Men with low peak bone mass are more vulnerable than those who achieved a higher peak bone mass in early adulthood. Peak bone mass and subsequent bone loss are affected by genetics, nutrition, exercise, alcohol consumption, smoking, disease, and medication use. Hypogonadal men and men treated with glucocorticoids are at markedly increased risk for spine fracture, especially as they age and bone resorption is superimposed on age-related changes. Evaluation of osteoporosis in men should include, at minimum, measurements of gonadal function (if unknown), nutritional status, calcium homeostasis, and thyroid function. Hypogonadal men should respond to testosterone replacement therapy. Men with high-turnover osteoporosis should respond to osteoclast-inhibitor therapy, and men with decreased osteoblast function should respond to stimulators of bone formation. Long-term effects of the various treatments on the rate of hip fracture are unknown, and the degree to which osteoporosis in men can be reversed is unclear.

Mechanism of delayed hepatic glycogen synthesis after an oral galactose load vs. an oral glucose load in adult rats.

We have compared the effects of administration of oral galactose or glucose (1 g/kg) to 24-h fasted rats to examine the mechanism by which galactose regulates its own incorporation into liver glycogen in vivo. Liver glycogen increased to a maximum more slowly after galactose than after glucose administration (0.14 vs. 0.29 mumol.g liver-1.min-1). Glycogen accumulation after the galactose load was 70% of that after the glucose load (149 vs. 214 mumol), and the net increase in liver glycogen represented the same proportion (24 vs. 22%) of added carbohydrate after urinary loss of galactose was accounted for. Slower glycogen accumulation after galactose vs. glucose loading could not be explained by galactosuria, by differences in the active forms of synthase or phosphorylase, by end product (glycogen) inhibition of synthase phosphatase, or by different concentrations of the known allosteric effectors of synthase R plus I and phosphorylase a. Similar increases in glucose 6-phosphate were observed after both hexoses. AMP and ADP increased only transiently after galactose administration, and ATP, UTP, and Pi concentrations were unchanged. The UDP-glucose concentration decreased, whereas the UDP-galactose concentration increased two- to threefold after galactose but not glucose administration. The UDP-glucose pyrophosphorylase reaction is inhibited competitively by UDP-galactose. This could explain the decreased UDP-glucose concentration and the reduced rate of glycogen synthesis after galactose was given.

Hepatic uptake and metabolism of oral galactose in adult fasted rats.

Galactose is incorporated into glycogen by a different metabolic route than glucose and fructose, the other major dietary monosaccharides. Oral galactose (4 g/kg) was given to 24-h-fasted adult rats to 1) compare quantitatively the disposition of galactose with that of glucose and fructose; 2) examine the effects of galactose on hepatic utilization of other metabolic fuels; and 3) examine circulating and liver galactose concentrations to determine whether net hepatic uptake of galactose, like glucose, occurs against a concentration gradient. Galactose absorption, hepatic blood flow, portal venous, arterial, hepatic venous, and liver concentrations of galactose, glucose, lactate, and alanine, and hepatic glycogen concentrations were measured at intervals up to 240 min. Concentrations entering and exiting the liver, hepatic intracellular concentrations, and net hepatic uptake/output were calculated. Galactose concentration entering the liver increased to a peak of 18.8 +/- 0.8 mumol/ml plasma water at 60 min and then decreased but remained above the control value. Liver galactose concentration increased dramatically from 0.28 +/- 0.04 to 21.2 +/- 1.1 mumol/ml liver water and exceeded plasma concentrations, even during the 1st 120 min when concentration gradients across the liver indicated net galactose extraction. Whole blood galactose concentrations initially were lower and then exceeded plasma concentrations, indicating that erythrocytes maintained galactose concentrations exceeding those in plasma. The data suggest that the hepatic and erythrocyte transport systems for galactose represent active mechanisms. Fifty-one percent of absorbed galactose was lost in urine; 18% of the remaining galactose load could be accounted for by net glycogen accumulation. Net increases in galactose, lactate, and alanine uptake could account for the glycogen synthesized but not for the net hepatic glucose output, which changed very little (6% increase).

Gynecomastia and cirrhosis of the liver.

Hepatic cirrhosis is frequently listed as a cause of gynecomastia. We found previously that in hospitalized men the prevalence of gynecomastia was correlated with body mass index and with age. The mean body mass index and the prevalence of gynecomastia in the cirrhotic subjects (nonedematous) did not differ from those in the overall population. Because more severely cirrhotic subjects with ascites, peripheral edema, or both usually are thin, we examined 18 more severely cirrhotic subjects and 18 nonobese (mean body mass index, 20.9 +/- 0.6 kg/m2), age-matched control subjects for the prevalence of palpable gynecomastia. Total testosterone, free testosterone, total estrogen, and estradiol concentrations also were measured. Fifty percent of the control subjects had gynecomastia. Breast tissue diameter was correlated with body mass index. The prevalence of gynecomastia in the cirrhotic subjects was 44%. In these subjects no significant correlation was noted between breast tissue diameter and body mass index, presumably because the body mass index was increased owing to fluid retention. The results could not be accounted for based on medications. Serum free testosterone concentrations were lower in the cirrhotic patients than in the controls (0.11 +/- 0.02 vs 0.22 +/- 0.03 nmol/L). The total estrogen-free testosterone ratio was higher in cirrhotic patients (10.3 +/- 2.5 vs 2.6 +/- 0.5), as was the estradiol-free testosterone ratio (2.2 +/- 0.7 vs 0.5 +/- 0.1). These ratios did not differ significantly in cirrhotic subjects with and without gynecomastia. Therefore, these data indicate that factors other than the estrogen-testosterone ratio are playing a role in the development of gynecomastia in both cirrhotic subjects and controls or that breast tissue sensitivity to an elevated estrogen-testosterone ratio is highly varible.

Disposition of a glucose load in fed rats and rats adapted to a high-carbohydrate diet.

Current evidence suggests that, during the transition from the fasted to the fed state, liver glycogen is synthesized primarily from gluconeogenic precursors rather than from glucose unless the circulating glucose concentration is high. In the fed state the glucose concentration already is elevated. We aimed to determine whether administration of an additional oral glucose load (4 g/kg) to chow- or high-carbohydrate diet-adapted (CHO) rats would further increase the glucose concentration and result in increased direct glucose uptake. In the chow- and CHO-fed rats, 70 and 98% of the administered glucose was absorbed by 120 min. In the chow-fed rats the glucose concentration entering the liver increased by only 1.0 mM from 8.0 to 9.0 mM; no net hepatic glucose uptake was observed. In the CHO-adapted rats the entering glucose concentration increased transiently by 3.5 mM from 8.0 to 11.5 mM. This was associated with net glucose uptake, which continued until the entering glucose concentration fell below 9.5 mM, the entering glucose concentration threshold above which net glucose uptake was observed previously in fasted rats. Net hepatic glucose uptake could not be correlated with insulin or hepatic intracellular glucose concentrations. Net glycogen synthesis did not occur in either group. We could not account for the absorbed glucose by the rise in portal glucose concentrations or by increased muscle glycogen deposition. The fate of much of the absorbed glucose remains unknown.

Hyperthyroxinemia in patients receiving thyroid replacement therapy.

Eleven patients, with a history of hypothyroidism, who had hyperthyroxinemia and an elevated free thyroxine index but normal serum triiodothyronine concentrations on levothyroxine replacement underwent levothyroxine dose reduction at three-month intervals until the free thyroxine index fell into the normal range. All were clinically euthyroid throughout. Normalization of the thyrotropin response to thyrotropin-releasing hormone occurred concomitantly, indicating correction of subtle hyperthyroidism. The mean thyroxine dose decreased from 161 micrograms/d (2.06 micrograms/kg) to 120 micrograms/d (1.51 micrograms/kg). The resting heart rate fell in eight of 11 patients (P less than .02). The left ventricular ejection fraction decreased in eight of 11 patients, although the decrease was not statistically significant. Considering the sensitivity of pituitary, cardiac, and bone tissue to even a small excess of thyroxine over time, hyperthyroxinemia associated with an elevated free thyroxine index should be corrected even in patients taking levothyroxine replacement who are clinically euthyroid and whose serum triiodothyronine concentrations are within normal limits.

Relationship of hepatic glucose uptake to intrahepatic glucose concentration in fasted rats after glucose load.

Glucose concentration gradients across the liver and hepatic blood flow were measured to characterize the relationship of hepatic glucose uptake to hepatic glucose concentration for 240 min after administration of a large oral glucose load to fasted rats. Extraction of glucose occurred only transiently, from 20 to 80 min after glucose administration. The liver changed from net glucose output to net glucose removal only when the intracellular hepatic glucose concentration exceeded 12.5 mumol/ml water. Even when arteriovenous glucose concentrations gradients were compatible with net direct hepatic uptake of glucose, the hepatic glucose concentration always exceeded the inflow glucose concentration. These data indicate that direct glucose uptake occurred against a concentration gradient when the liver is considered as a whole. The hepatic intracellular-to-extracellular glucose concentration gradient changed very little, suggesting that this is not being regulated by glucose, insulin, or other effectors. The mechanism by which the hepatic glucose concentration and net hepatic glucose uptake versus output are coordinated is unknown. The rate of glycogen synthesis was linear for 120 min after administration of the glucose load. This occurred in the presence of direct uptake of glucose early in the time course and later in the presence of net glucose output by the liver. Net direct uptake of glucose by the liver could account for, at most, 37-55% of the glycogen formed. Fractional extraction of both lactate and alanine decreased after glucose was given, but net hepatic uptake of these metabolites could account for 33-49 and 7-10%, respectively, of the glycogen formed, depending on plasma versus blood water flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of glycogen synthesis in the liver.

The glycogen synthase-mediated reaction is rate-limiting for glycogen synthesis in the liver. Glycogen synthase has been purified essentially to homogeneity and has been shown to be a dimer composed of identical subunits. It is regulated by a phosphorylation-dephosphorylation mechanism, catalyzed by kinases and a phosphatase. The subunits of synthase D, the most phosphorylated form, each contain approximately 17 phosphates. The subunits of synthase I, the least phosphorylated form, each contain 14 phosphates. Thus, during the transition between these two forms, a net of three phosphoryl groups is added or removed. In synthase D, six of the phosphates are alkali-labile. In synthase I, three of the phosphates are alkali-labile. Therefore, all of the phosphorylation sites important in the interconversion of these two forms are alkali-labile (attached to serine or threonine residues). In short-term experiments using isolated hepatocytes, [32P]phosphate was only incorporated into the alkali-labile sites and the phosphate in these sites was shown to turn over rapidly. Glucose addition, which is known to reduce the proportion of synthase in the D form when assayed kinetically, also reduced the [32P]phosphate content. Glucagon addition, which increases the proportion of synthase in the D form, increased it. These changes do not appear to be site-specific. Ingestion or administration of fructose, or galactose, as well as glucose, result in a shift in synthase equilibrium in favor of the less phosphorylated forms. Possible mechanisms by which synthase phosphatase activity may be increased after ingestion of glucose or fructose, and thus shift the equilibrium in favor of the less phosphorylated forms, are discussed. The mechanism by which galactose may stimulate the phosphatase reaction is completely unknown.

Effects of graded intravenous doses of fructose on glycogen synthase in the liver of fasted rats.

We have examined in fasted rats the effects of graded doses of intravenous fructose (50 to 500 mg/kg) in order to determine potential mechanisms by which different concentrations of fructose reaching the liver may modify the activity of glycogen synthase (and phosphorylase). With increasing fructose doses the % synthase I increased threefold to a maximum at a dose of 125 mg/kg and then decreased progressively after higher fructose doses were given. The % phosphorylase a decreased by 30% to a minimum at a dose of 125 mg/kg but increased with higher doses to 370% of the control values. Both the % synthase I and the % phosphorylase a were elevated above the control values at fructose doses of 175 to 225 mg/kg. The increase in % synthase I after low doses of fructose occurred with a significant increase in glucose-6-P but no significant change in hepatic fructose, glucose, UDPglucose, ATP/Mg++, Pi, cAMP, plasma insulin, or glucagon concentrations. The reciprocal decrease in % synthase I and increase in % phosphorylase a occurred despite increases in glucose and glucose-6-P, at fructose doses resulting in no change in ATP/Mg++, Pi or cAMP, and only a small increase (0.39 mmol/L) in the fructose-1-P concentration. We propose that activation of synthase phosphatase by a rise in the glucose-6-P concentration is responsible for the increase in % synthase I after low doses of fructose. The mechanism by which higher fructose doses overcome the expected activation of synthase phosphatase by glucose and glucose-6-P and a decreased ATP/Mg++ ratio is uncertain.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of zinc supplementation in type II diabetes mellitus.

Zinc is required for normal immune function and taste acuity and enhances the in vitro effectiveness of insulin. Impaired immune function and taste have been reported in diabetic subjects, and decreased serum zinc levels and hyperzincuria occur in some diabetic subjects and animals. Subjects with type II diabetes were examined to determine whether the similar effects of zinc depletion and diabetes are causally related. Low serum zinc levels were found in 16 of 180 subjects (9 percent). There was no correlation between serum zinc and glycosylated hemoglobin levels. Natural killer cell activity did not differ between diabetic subjects (n = 28) and control subjects (n = 38) and did not correlate with serum zinc levels. T lymphocyte response to phytohemagglutinin was lower in diabetic subjects than in control subjects (70 +/- 10 versus 103 +/- 7 X 10(3) counts per minute) but was not lowest in those with the lowest zinc levels. Taste thresholds for hydrochloric acid, sucrose, sodium chloride, and urea were elevated in diabetic subjects (n = 28) versus control subjects (n = 10), but thresholds did not correlate with glycosylated hemoglobin or serum zinc levels. Zinc supplementation in nine diabetic subjects had no effect on the glycosylated hemoglobin level, natural killer cell activity, or taste thresholds, but it did increase mitogen activity in those with the lowest initial phytohemagglutinin responses. It is concluded that zinc deficiency occurs in a subset of subjects with type II diabetes but is not related to diabetes control and does not explain decreased taste acuity. Zinc deficiency may play a role in abnormal immune function in type II diabetes mellitus.

Mechanism of stimulation of liver glycogen synthesis by fructose in alloxan diabetic rats.

In diabetic animals and humans, stimulation of liver glycogen synthesis has been reported after administration of a large parenteral fructose load. The effects of an oral fructose load have not been examined previously. In the diabetic state, glycogen synthase phosphatase activity is reduced, and synthase D (the inactive form) is a poor substrate for the phosphatase. Thus, activation of synthase to the synthase R and synthase I (R + I) (active) forms by fructose would not be expected. We have determined that oral fructose administration does stimulate glycogen synthesis and have examined the mechanism by which this is accomplished. In 24-h-fasted alloxan diabetic rats, basal liver glycogen was higher than in normal rats (8.3 +/- 1.8 vs. 3.0 +/- 0.5 mg/g wet wt). After fructose (4 g/kg) was given, the initial rate of glycogen synthesis was normal in diabetic rats, but total glycogen synthesis was reduced. By 240 min, liver glycogen increased to 18 +/- 4.0 mg/g wet wt in diabetic rats versus 30.5 +/- 1.5 mg/g wet wt in normal rats. Synthase R + I was low and did not increase significantly (0.063 +/- 0.006 to 0.064 +/- 0.010 U/g wet wt) after fructose administration to the diabetic animals. Phosphorylase a did not decrease significantly during the period of active glycogen synthesis. In the diabetic rats, glucose-6-phosphate increased by 84% (0.103 +/- 0.010 to 0.184 +/- 0.020 mumol/g wet wt) within 10 min and remained elevated above the control level. UDPglucose decreased from 0.336 +/- 0.013 to 0.271 +/- 0.011 mumol/g wet wt at 10 min and remained below the control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of dietary versus parenteral fructose.

Fructose has been considered as an alternative sweetener to sucrose because it results in less glycemia when given to normal subjects or to those with mild noninsulin-dependent diabetes mellitus. Oral fructose also results in efficient glycogen synthesis. However, multiple hepatotoxic effects have been reported following parenteral fructose administration. We have examined the effects of large oral fructose and glucose loads (4 g/kg) and of graded intravenous fructose doses (50-500 mg/kg) on hepatic metabolism and glycogen synthesis in normal, fasted rats. Fructose was absorbed more slowly than glucose when given by gavage (59% vs 91% absorbed in 120 min). Oral fructose administration resulted in greater liver and muscle glycogen synthesis, despite smaller increases in plasma glucose and insulin concentrations, than was found after oral glucose administration. Increases in percent glycogen synthase I (active form) occurred after both oral fructose and glucose loads (67% vs 115% increase). There was no evidence of hepatotoxicity even after a very large oral fructose load. When small (less than or equal to 125 mg/kg) iv doses of fructose were given, the portal vein fructose concentration remained less than or equal to that found after oral fructose administration (1.1 mM). The percent synthase I increased up to threefold, and there was no evidence of hepatotoxicity. Larger iv doses resulted in a fall in percent synthase I, an increase in percent phosphorylase a, and inorganic phosphate and nucleotide depletion. We conclude that the slow absorption of an oral fructose load prevents hepatotoxic effects and permits efficient glycogen synthesis.

Effect of insulin administration on cardiac glycogen synthase and synthase phosphatase activity in rats fed diets high in protein, fat or carbohydrate.

Rats were fed a 70% carbohydrate, 70% protein, 70% fat, or a standard purified diet for 7 d to determine the effect of the diet on heart glycogen synthase response to an acute insulin challenge. Rats fed the high protein or the high fat diets, i.e., the carbohydrate-free diets, exhibited insulin resistance as evidenced by higher plasma glucose levels following insulin administration when compared to rats fed high carbohydrate or standard diet. The diets had no effect on the initial proportion of synthase in the active or I form. Insulin injection resulted in an increase in the proportion of synthase in the active form in rats fed the standard, high carbohydrate or high protein diets, but not in rats fed the high fat diet. Synthase phosphatase activity was similar in rats fed one of the four diets compared to rats fed a nonpurified diet. Thus the lack of synthase response to insulin in fat-fed rats was not due to diminished synthase phosphatase activity. Neither the diets nor insulin administration had any effect on the proportion of phosphorylase in the active or a form. Cardiac glycogen was significantly lower in rats fed the high fat diet than in those fed the standard diet. The latter was a surprising observation since the high fat diet was used to simulate a starved state and cardiac glycogen concentrations increase with starvation.

Gynecomastia in a hospitalized male population.

Two hundred fourteen hospitalized adult men, aged 27 to 92, were examined for the presence of palpable gynecomastia. The overall prevalence was 65 percent. Gynecomastia was bilateral in all but 11 subjects. The prevalence was greatest in the 50 to 69-year-old group (72 percent). It was lower in the 70- to 89-year-old (47 percent, p less than 0.01) and the 30- to 49-year-old (54 percent, p less than 0.05) groups. The prevalence of gynecomastia increased with body mass index. More than 80 percent of those with a body mass index of 25 kg/m2 or greater had gynecomastia. The diameter of breast tissue also increased with increasing body mass index (r = 0.52, p less than 0.001). The decreased prevalence of gynecomastia after the seventh decade could be explained by the lower body mass index in this group. The youngest group did not have a lower body mass index; an independent age factor appeared to be present. Because of the high overall prevalence of gynecomastia, independent effects of diseases or medications could not be determined. It is concluded that palpable bilateral gynecomastia is present in most older men, is correlated with the amount of body fat, and does not require clinical evaluation unless symptomatic or of recent onset.

Metabolic effects of oral fructose in the liver of fasted rats.

Twenty-four-hour-fasted rats were given fructose (4 g/kg) by gavage. Fructose absorption and the portal vein, aorta, and hepatic vein plasma fructose, glucose, lactate, and insulin concentrations as well as liver fructose and fructose 1-P, glucose, glucose 6-P, UDPglucose, lactate, pyruvate, ATP, ADP, AMP, inorganic phosphate (Pi), cAMP, and Mg2+, and glycogen synthase I and phosphorylase alpha were measured at 10, 20, 30, 40, 60 and 120 min after gavage. Liver and muscle glycogen and serum uric acid and triglycerides also were measured. Fifty-nine percent of the fructose was absorbed in 2 h. There were modest increases in plasma and hepatic fructose, glucose, and lactate and in plasma insulin. Concentrations in the portal vein, aorta, and hepatic vein plasma indicate rapid removal of fructose and lactate by the liver and a modest increase in production of glucose. The source of the increase in plasma lactate is uncertain. Hepatic glucose 6-P increased twofold; UDPglucose rose transiently and then decreased below the control level. Fructose 1-P increased linearly to a concentration of 3.3 mumol/g wet wt by 120 min. There was no change in ATP, ADP, AMP, cAMP, Pi, or Mg2+. Serum triglycerides and uric acid were unchanged. Glycogen synthase was activated by 20 min without a change in phosphorylase alpha. This occurred with a fructose dose that did not significantly increase either the liver glucose or fructose concentrations. Liver glycogen increased linearly after 20 min, and glycogen storage was equal in liver (38.4%) and muscle (36.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of oral glucose in the liver of fasted rats.

Twenty-four-hour-fasted rats were given glucose (4 g/kg) by gavage. Glucose absorption and portal and peripheral plasma glucose, lactate, and insulin concentrations, as well as liver glucose, UDPglucose, glucose-6-P, lactate, ATP, and inorganic phosphate (Pi), and % glycogen synthase I and % phosphorylase a were measured at 10, 20, 30, 40, 60, and 120 min after the glucose was given. Liver and muscle glycogen also were measured. Ninety-one percent of the glucose load had disappeared from the gut in 2 h. Despite increased plasma glucose and insulin levels the liver continued to produce glucose. Lactate produced in the periphery was the major substrate for gluconeogenesis, and lactate utilization could account for the hepatic glycogen synthesized. Glucose ingestion did not affect lactate production by the splanchnic bed. In the liver glucose-6-P was transiently increased; UDP glucose decreased after glucose administration. ATP and Pi were unchanged. Glycogen synthase was activated by 20 min without a significant change in phosphorylase a. Hepatic glycogen increased linearly after 20 min. Total glucose storage as glycogen was similar in liver (20%) and muscle (19%). We could account for 41% of the glucose absorbed as glycogen, unmetabolized glucose, or glucose metabolites. Most of the remainder probably was oxidized.

Adrenocortical hyperactivity in newly admitted alcoholics: prevalence, course and associated variables.

After initial screening of 269 consecutive Psychiatry Service admissions suggested adrenal stimulation in alcoholics, 52 consecutive newly-admitted alcoholics were intensively studied in order to determine the extent of adrenal hyperactivity, how quickly it resolved and the factors associated with it. While 21% failed to show suppression of cortisol at either 0800 or 1600 hr the day following administration of dexamethasone (1 mg) at 2300 hr, no patient showed both clinical and biochemical evidence of alcoholic pseudo-Cushing's syndrome, and all patients suppressed normally eight days later. Analysis of a variety of variables, including several measures of recent alcohol consumption, alcohol withdrawal and depression failed to show significant association with nonsuppression. The DST should be interpreted cautiously in alcohol abusers during the first 10-14 days following admission. Persistent nonsuppression, however, is probably not due to alcohol abuse.