Dietary components that regulate serum somatomedin-C concentrations in humans.

Dietary components responsible for the regulation of somatomedin-C in humans were assessed in five adult volunteers of normal weight who were fasted for 5 d on three occasions, then refed three diets of differing composition. The serum somatomedin-C decreased from a mean prefasting value of 1.85 +/- 0.39 U/ml (+/- 1 SD) to 0.67 +/- 0.16 U/ml at the end of fasting (P less than 0.005). After refeeding for 5 d with a normal diet, the mean serum somatomedin-C increased to 1.26 +/- 0.20 U/ml. A protein-deficient (32% of control), isocaloric diet resulted in a significantly smaller increase, to a mean value of 0.90 +/- 0.24 U/ml (P less than 0.05). A diet deficient in both protein and energy led to a further fall 0.31 +/- 0.06 U/ml. The changes in somatomedin-C during fasting and refeeding correlated significantly with mean daily nitrogen balance (r = 0.90). We conclude that both protein and energy intake are regulators of serum somatomedin-C concentrations in adult humans, and energy intake may be of greater importance. The correlation between changes in somatomedin-C and nitrogen balance suggests that the former are directly related to changes in protein synthesis and may be helpful in assessing the response to nutritional therapy.

Abnormalities in thyroid function tests in patients admitted to medical service.

Serum thyroid hormone, thyrotropin (TSH) and thyroxine-binding globulin (TBG) concentrations, free thyroxine index values, and free thyroxine concentrations were measured at the time of admission in all 77 patients hospitalized on a medical service on four separate days. Serum thyroxine (T4) concentrations and serum free T4 index values were decreased in 19.5% and 11.7%, respectively, and increased in 3.9% and 11.7%, respectively; serum free T4 concentrations were decreased in 6.8% and increased in 5.4%. Six patients (7.8%) had increased serum TSH concentrations. Serum triiodothyronine (T3) concentrations were decreased in 26.0% and reverse triiodothyronine (rT3) concentrations were increased in 29.9%. None had manifestations of thyroid disease. These results indicate that available thyroid function tests may give misleading results in patients with nonthyroid illness and suggest that caution be exercised in diagnosing thyroid disease in hospitalized patients.

Insulin-like growth factor-binding protein-3 proteolysis is induced after elective surgery.

The insulin-like growth factors (IGFs) are bound to several binding proteins (IGFBPs) that appear to regulate IGF transport, receptor binding, and action. The concentrations of these peptides are altered by catabolic conditions. To determine if IGF-I and IGFBP levels change after surgery, sera were obtained from 16 patients before and after cholecystectomy. Immunoreactive IGF-I measured in plasma samples from which IGFBPs had been extracted did not change postoperatively. In contrast, IGF-I determined in unextracted samples increased roughly 3-fold postoperatively, presumably due to changes in IGFBPs. Two days postoperatively, IGFBP-3 levels, determined by ligand blot, averaged 36% of preoperative values, whereas levels of IGFBP-2 and a 24,000 mol wt IGFBP did not change significantly. Similarly, by immunoblot, intact IGFBP-3 was decreased 84.2 +/- 20.2%, and a 31,000 mol wt IGFBP-3 fragment increased 57.5 +/- 47.4% postoperatively. Coincubation of postoperative, but not preoperative, sera with control sera resulted in a significant decrease in IGFBP-3 and production of proteolytic fragments. IGFBP-3 proteolytic activity in postoperative sera was markedly inhibited by antipain, Na-p-tosyl-L-lysine chloromethyl ketone, phenylmethylsulfonylfluoride, aprotinin, o-phenanthroline, and EDTA, but not by leupeptin or N-tosyl-L-phenylalanine chloromethyl ketone. This pattern of inhibition is consistent with a metal-dependent trypsin-like serine protease. We speculate that proteolysis of IGFBP-3 may alter tissue uptake of IGF-I and thereby help to counteract the catabolic state caused by surgery.

Efficacy and safety of reformulated, micronized glyburide tablets in patients with non-insulin-dependent diabetes mellitus: a multicenter, double-blind, randomized trial.

The subjects were 206 patients (123 men, 83 women) with non-insulin-dependent diabetes mellitus, aged 33 to 80 years. For at least 4 weeks prior to the study each subject had been taking 5-mg tablets of original, nonmicronized glyburide (Micronase tablets) in doses of 5, 10, 15, or 20 mg daily. In a double-blind 12-week study, the subjects were randomly assigned to continue receiving 5-mg tablets of original glyburide or to substitute 3-mg tablets of reformulated, micronized glyburide (Glynase PresTab tablets) for the original tablets. Glyburide tablets had been reformulated to improve their bioavailability. Baseline mean fasting serum glucose levels in the groups taking reformulated and original glyburide were 169.3 and 168.3 mg/dl, respectively; at study end point, their respective serum glucose levels were 186.0 and 177.0 mg/dl. The differences between groups were not significant; in both groups, however, end point glucose levels were significantly higher than baseline levels. Baseline hemoglobin A1C levels in the groups taking reformulated and original glyburide were both 7.6%; at study end point, hemoglobin A1C levels had improved slightly in each group to 7.4% and 7.5%, respectively. The differences between and within groups at end point were not significant. No between-group differences at baseline or at end point were found in mean levels of postprandial serum glucose, fasting C-peptide, or postprandial C-peptide. Medical events experienced by the subjects in the two groups were similar in nature and number. Changes in other laboratory test results, vital signs, and weight were not clinically meaningful.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in plasma somatomedin-C in response to ingestion of diets with variable protein and energy content.

We have attempted to determine the relative importance of dietary intake of protein and energy in restoring plasma immunoreactive somatomedin-C (Sm-C) concentrations after fasting. Ten healthy human volunteers were fasted for 5 days, then divided into two refeeding groups. One group (variable energy) was refed 1.0 g protein/kg ideal body weight, and in 9-day sequences, 11, 18 and 25 kcal of energy/kg. The other group (variable protein) was given 35 kcal energy/kg, and in 9-day sequences, 0.2, 0.4, and 1.0 g protein/kg. When subjects were refed the variable energy diets there was no significant increase in Sm-C at 11 kcal/kg (0.47 +/- 0.13 to 0.45 +/- 0.12 U/ml), suggesting that there is a threshold energy requirement below which optimal protein intake is not sufficient to raise the Sm-C. When subjects were refed 18 and 25 kcal/kg, it became apparent that the more energy added to the diet, the greater the absolute concentration of Sm-C attained (0.66 U/ml on 18 kcal/kg and 0.97 U/ml on 25 kcal/kg). Sm-C correlated with nitrogen balance (r = 0.58) during refeeding with the variable energy diets and was a good indicator of acute directional change in nitrogen balance. However, Sm-C was not a reliable indicator of nitrogen repletion, since it rose almost to control levels on the 25 kcal/kg diet while nitrogen balance remained slightly negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyrotoxicosis in the critically ill.

The thyrotoxic patient offers a considerable challenge to the critical care physician because the "obvious" diagnosis often will be a cardiac (or other nonthyroidal) problem, but the "correct" diagnosis will be an endocrinologic one. The importance of considering the diagnosis of thyrotoxicosis in any patient with tachyarrhythmias, new-onset congestive heart failure, weight loss, or change in mental status cannot be overstated. Treatment for presumed thyroid disease sometimes will have to be initiated prior to the availability of the results of diagnostic tests. Timely and appropriate treatment of the thyroid problem is vital for a successful outcome in treating patients with thyrotoxicosis.

Frequency and impact of SMBG on glycemic control in patients with NIDDM in an urban teaching hospital clinic.

Few published reports have documented the value of SMBG on glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), and no reports have evaluated predominantly African American patients who are at high risk for NIDDM and associated complications. In this study a 13-item survey was given to 98 patients with NIDDM to assess the frequency of self-monitoring of blood glucose (SMBG) and its impact on glycemic control. Sixty-one patients performed SMBG and 37 did not. More SMBG testers were taking insulin compared with the nontesters. GHb was comparable between groups. Among the testers there was no difference in mean GHb values based on the frequency of SMBG. Most testers performed SMBG before meals (93%) and recorded their values (85%); many had difficulty obtaining a good blood sample (30%). The most common reason for not testing was cost of supplies (77%). Performance of SMBG in these NIDDM patients was not associated with better glycemic control. Cost was a prohibitive factor for the nontesters.

Thyroid dysfunction in the severely ill and elderly. Forget the classic signs and symptoms.

Manifestations of thyrotoxicosis and hypothyroidism are often ill-defined in elderly and seriously ill patients, and signs and symptoms may suggest a nonendocrine disease process instead. It is vitally important that physicians be aware of the possibility of thyroid disease in such patients. Failure to suspect the diagnosis may result in improper treatment and use of invasive diagnostic tests that not only fail to yield helpful results but also are potentially detrimental to the outcome. It is also essential to be able to distinguish between test abnormalities that indicate primary thyroid dysfunction and those that reveal an adaptive response to nonthyroidal illness.

Endocrine emergencies. Recognizing clues to classic problems.

Although the possibility of an endocrine emergency occurring in a primary care setting may seem remote, awareness of such emergencies is crucial for appropriate management. While some symptoms are specific to classic endocrine disorders, other symptoms, such as nausea, vomiting, and diarrhea, are so general that the diagnosis may not be considered initially. In these situations, careful and thoughtful diagnostic studies can be lifesaving.

Clinical trial evidence for the cardioprotective effects of omega-3 fatty acids.

The notion that marine omega (w)-3 fatty acids might have beneficial cardiovascular effects was first suggested by epidemiologic studies in Greenland Inuits published in the late 1970s. These simple observations spawned hundreds of other studies, the confluence of which strongly suggests a true cardioprotective effect of w-3 fatty acids. The strongest confirmation has come from the publication of three randomized clinical trials, all of which reported benefits to patients with preexisting coronary artery disease. The most convincing of these was the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI)-Prevezione study, in which 5654 patients with coronary artery disease were randomized to either w-3 fatty acids (850 mg/d) or usual care. After 3.5 years, those taking the w-3 fatty acids had experienced a 20% reduction in overall mortality and a 45% decrease in risk for sudden cardiac death. These findings support the view that relatively small intakes of w-3 fatty acids are indeed cardioprotective, and suggest that they may operate by stabilizing the myocardium itself.

Rifampicin-induced adrenal insufficiency in the acquired immunodeficiency syndrome: difficulties in diagnosis and treatment.

Rifampicin, an antituberculous drug, causes increased hepatic metabolism of steroid hormones. We report the case of a patient with the acquired immunodeficiency syndrome treated with rifampicin who had a 'normal' screening test for adrenal insufficiency, yet had clinical evidence of adrenal failure. Diagnostic testing could not be completed due to lack of clinical response to dexamethasone. Both of these findings are due to the unique effects of rifampicin on steroid metabolism.

Dialyzable factor in human serum of platelet origin stimulates endothelial cell replication and growth.

Porcine aortic endothelial cells were isolated and maintained in Dulbecco's modified Eagle's medium (DME medium)/10% citrate-treated human plasma. They were stimulated by DME medium/10% human serum to grow from a density of 10,100 +/- 500 per well to a final density of 83,000 +/- 1,800 per well over a 9-day period. On the other hand these cells grew poorly (11% increase) in DME medium/10% human platelet-poor plasma prepared without chelating agents and containing platelet factor 4 at 18 ng/ml by radioimmunoassay. Dialysis of the human serum (M(r) cutoff, 3,500) eliminated all the stimulatory activity. The activity recovered from the dialysate stimulated growth when added to endothelial cultures in conjunction with either dialyzed serum or platelet-poor plasma alone. The dialyzable factor could be obtained directly from platelets; both acetic acid extracts and boiled NaCl extracts stimulated porcine aortic endothelial cell replication. Gel filtration chromatography on Sephadex G-15 showed that the endothelial growth factor had a molecular weight of 700. Partially purified material induced a concentration-dependent stimulation of porcine aortic endothelial cell replication in the presence of DME medium alone; however, simultaneous incubation with platelet-poor plasma resulted in a much greater response. Fibroblast growth factor isolated from bovine brain was found to be mitogenic only in the presence of nondialyzed serum or of the dialyzable factor together with plasma. In the absence of this serum factor, fibroblast growth factor had no effect. We conclude that human serum contains a potent endothelial cell mitogen of platelet origin. Human plasma that is devoid of platelet content does not stimulate endothelial cell growth. This growth factor may be an important stimulant of the endothelial cell response to vascular wall injury.

Unilateral adrenal hyperplasia as a cause of primary aldosteronism.

We have described a patient with unilateral adrenal hyperplasia, a rare cause of primary aldosteronism, and reviewed the literature on this subject. The treatment of this disorder appears to be surgical. Whether its pathogenesis is related to the more common varieties of primary aldosteronism is open to speculation.

Troglitazone-induced hepatic failure leading to liver transplantation. A case report.

BACKGROUND: Troglitazone is a new drug for the treatment of type 2 diabetes. Although mild liver injury occurred in 1.9% of participants in controlled trials, the U.S. Food and Drug Administration has received reports of five postmarketing cases of severe liver disease that resulted in death or liver transplantation. OBJECTIVE: To report the clinical and histopathologic characteristics of a patient with troglitazone-associated severe liver injury leading to transplantation. DESIGN: Case report. SETTING: Two university hospitals. PATIENT: A 55-year-old woman taking troglitazone, 400 mg/d, and insulin, 120 U/d. INTERVENTION: Discontinuation of troglitazone therapy, pretransplantation liver biopsy, and liver transplantation. RESULTS: Early nonspecific symptoms were attributed to other causes and were not evaluated. After the patient had used troglitazone for 3.5 months, massive loss of liver parenchyma and symptoms of liver failure developed, necessitating liver transplantation. CONCLUSION: Troglitazone may cause subfulminant liver failure.