Valerian Dias

Effects of Medium-Chain Triglyceride Feeding on Energy Balance in Adult Humans

In recent years, the metabolism of triglycerides has attracted much attention. Oxidation of fatty acids is an essential energy supply, especially when glucose supply is limited. In the present study, the effect of a 3-day high medium-chain triglyceride (MCT; 51% of calories), low carbohydrate intake on plasma glucose and amino acid, and urinary organic acid levels, including dicarboxylic and tricarboxylic acid cycle intermediates, was determined in eight normal adult volunteer subjects. Urine was collected at baseline and at 48 to 72 hours for amino acid and organic acid levels, and plasma collected at 0 and 72 hours for glucose and amino acid concentration. The MCT diet increased urinary levels of dicarboxylic acids (adipic 8-, suberic 65-, sebacic 284-fold) and keto acids (acetoacetate and beta-hydroxybutyrate, 67.5-fold); alanine and lactate were decreased 2.5- and 4-fold, respectively, while pyruvate, other amino acids and citric acid intermediates remained unchanged. Plasma amino acid levels were unchanged, while the plasma glucose levels decreased by 8% from baseline. The loss of calories as urinary dicarboxylic acids and keto acids, although increased during the MCT diet, was less than 1% of the daily caloric intake. The data suggest MCT sustain energy expenditure through medium-chain fatty acid (MCFA) oxidation with no decrease in citric acid cycle intermediates, while sparing protein oxidation.

Catheterization during adrenal vein sampling for primary aldosteronism: failure to use (1-24) ACTH may increase apparent failure rate.

“Successful” adrenal vein catheterization in primary aldosteronism (PA) is often defined by a ratio of >3:1 of cortisol in the adrenal vein vs the inferior vena cava. Non‐use of corticotropin (ACTH) during sampling may increase the apparent failure rate of adrenal vein catheterization due to lower cortisol levels. A retrospective study was performed on all patients with confirmed unilateral PA between June 2005 and August 2011. Adrenal vein sampling (AVS) included simultaneous bilateral baseline samples with repeat sampling 15 minutes after intravenous infusion of 250 μg of Cortrosyn (ACTH‐S). Successful catheter placement was judged as adrenal cortisol:IVC cortisol of >3:1, applied to both baseline and ACTH‐S samples and lateralization of aldosteronism was judged as normalized aldosterone/cortisol (A/C) ratio >3 times the contralateral A/C ratio. In ACTH‐S samples, 94% of right‐sided catheterizations were biochemically successful with 100% success on the left. Among baseline samples, only 47% of right‐ and 44% of left‐sided samples met the 3:1 cortisol criteria. However, 95% of apparent “failed” baseline cortisol sets still showed lateralization of A/C ratios that matched the ultimate pathology. Non–ACTH‐stimulated samples may be incorrectly judged as failed catheter placement when a 3:1 ratio is used. ACTH‐stimulated sampling is the preferred means to confirm catheterization during AVS.

Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia ☆

BACKGROUND Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference ranges for the normal salivary cortisol levels in healthy patients and patients with adrenal insufficiency. DESIGN AND METHODS Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency. RESULTS We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74-0.86, p<0.0001). The corresponding salivary cortisol equivalent to a serum cortisol of 500 nmol/L, using a linear-regression equation, was 16.7 nmol/L (95% CI 13.3-20.1 nmol/L, p=0.0001). A salivary cortisol of 13.3 nmol/L has a specificity of 89.3% to detect abnormal HPA function. Using the upper 95% CI result of salivary cortisol 20.1 yields a sensitivity of 87.5%. CONCLUSION With the present assay, adrenal insufficiency may be diagnosed with reasonable confidence if a random salivary cortisol is lower than 13.3 nmol/L and excluded if a random salivary cortisol is higher than 20.1 nmol/L. Future studies should correlate these thresholds with clinical outcomes.

Addison's Disease in Evolution: An Illustrative Case and Literature Review.

OBJECTIVE To present a case of symptomatic autoimmune adrenal insufficiency with initially normal serum cortisol and to caution about limitations of the current diagnostic algorithm for adrenal insufficiency, which does not reflect the pathophysiology of early disease. METHODS We describe the clinical presentation and relevant investigations of a patient ultimately found to have Addisons disease, which is followed by a focused review of the literature. RESULTS A 41-year-old Caucasian woman with autoimmune hypothyroidism, premature ovarian failure, and microscopic colitis presented with nausea, salt craving, increased skin pigmentation, and postural hypotension. Initial bloodwork revealed a normal morning cortisol of level of 19.2 μg/dL (normal, 7.2 to 25 μg/dL) but an adrenocorticotropic hormone (ACTH) level 10 times normal, at 513.6 pg/mL (normal, <52.5 pg/mL). Her potassium was normal, but her aldosterone level was 4.12 ng/dL (normal, 12.3 to 62.5 ng/dL) and her renin activity was increased (23.0 mg/dL/hour; normal, <6.0 mg/dL/hour). Six weeks after initial presentation, she was found to have anti-adrenal antibodies. It was not until 10 weeks after her initial symptomatic presentation that her morning cortisol level was found to be subnormal and a formal diagnosis of adrenal insufficiency was made. CONCLUSION The present case and literature review reveal that common diagnostic approaches will miss patients with (possibly symptomatic) early adrenal insufficiency. We suggest that serum ACTH level testing or tests of mineralocorticoid function be included in the initial step of investigation for suspected primary adrenal insufficiency.

Chapter 3 – Effect of Patient Preparation, Specimen Collection, Anticoagulants, and Preservatives on Laboratory Test Results

Various pre-analytical factors affect clinical laboratory test results, including patient preparation, specimen collection, anticoagulants, and preservatives used for collecting specimens. The most assessable specimens are blood and urine. For analysis using blood, important factors such as the presence of anticoagulants in plasma and in whole blood, hematocrit variability, and the differences in serum characteristics associated with blood coagulation should be considered. Optimal anticoagulant-to-blood ratio is crucial to prevent clot formation while avoiding interference with analyte measurement, including dilution effects associated with liquid anticoagulants. Other factors to consider regarding blood collection tubes include differences between plastic and glass surfaces, surfactants, tube stopper lubricants, and gel separators, which all affect analyte measurement. There are also pre-analytical factors that affect test results using urine specimens. These issues are addressed in this chapter.