Guest guest Posted February 9, 2009 Report Share Posted February 9, 2009 Hi Sonya, I hope you are aware that there are herbs in Isocort that stimulate the immune system. My bio-chemist doc warns against Ginseng, Echinacea, and other herbs that can cause the immune system to over act by stimulating the production of cytokines. He said they are contra-indicated in patients with autoimmune disorders, because these people need their AI system to calm down, not speed up thyroid destruction. --Bj > > My Dr did the test and my results came back border line but not out yet. She recommended me to start on Bezwecken IsoCort two piills, twice a day; in the am and at lunch. I can't thank her enough. Synthroid helps me feel better but not with being so tiered all the time, with IsoCort, I feel like I can pay attention and I don't want to fall sleep all the time. You don't need a prescription; I buy mine online. > Sent via BlackBerry by AT & T > > Measurement of cortisol in serum and saliva > > > Measurement of cortisol in serum and saliva > > Author > Lynnette K Nieman, MD Section Editor > Andre Lacroix, MD Deputy Editor > A , MD > > INTRODUCTION — Measurements of cortisol in serum--or occasionally > plasma--are extremely useful in the diagnosis of hypercortisolism and > adrenal insufficiency. It is important to appreciate the many factors > that can affect the serum cortisol concentration and in particular the > episodic secretion of cortisol and the resulting diurnal variation in > serum cortisol, which makes the interpretation of a single value > hazardous. Measurements of the salivary cortisol may offer some > advantages over measurements of serum cortisol. Methods of > interpretation of cortisol assays will be reviewed here. Their use in > the diagnosis of adrenal disorders is reviewed separately. (See > " Establishing the diagnosis of Cushing's syndrome " and see " Diagnosis > of adrenal insufficiency in adults " ). > > MEASUREMENT OF SERUM CORTISOL — Cortisol has been measured in serum by > several methods. Although many of them are no longer in routine use, > the important assays are mentioned to permit one to interpret the > older literature. > > Methods of measurement > > Porter-Silber chromogens — Serum cortisol was first measured by assay > of Porter-Silber chromogens (17,21-dihydroxy-20-ketosteroids, referred > to as 17-hydroxycorticosteroids, or 17-OHCS) [1] . This method is no > longer used. > > Competitive protein-binding assay — This assay uses competition for > binding sites on cortisol-binding globulin (CBG, or transcortin) to > quantify cortisol [2,3] . Its advantage is lack of drug interference; > its disadvantage is that prednisolone and several endogenous steroids, > some of which may be increased in pregnancy, adrenal carcinoma, > congenital adrenal hyperplasia, and after administration of adrenal > enzyme inhibitors, bind to CBG and falsely elevate serum cortisol > values. Interfering steroids can be removed before assay by solvent > partition or thin layer chromatography (TLC). > > Fluorometric assay — This assay exploits the fluorescence of > 4-11-beta, 21-dihydroxy-3,20-ketosteroids (11- hydroxycorticosteroids, > or 11-OHCS) in sulfuric acid and alcohol [4] . Cortisol and > corticosterone are detected by this assay; potent synthetic > glucocorticoids are not. Its advantages are simplicity and relative > specificity; its disadvantage is that spironolactone, quinine, > quinidine, niacin, and benzoyl alcohol also fluoresce in those > solvents and therefore falsely elevate cortisol values. > > Radioreceptor assay — This assay uses the type II glucocorticoid > cytosol receptor as a cortisol-binding agent [5] . Its advantage is > its specificity for bioactive steroids, including synthetic > glucocorticoids; its disadvantage is the limited supply and > instability of the receptor. As a result, this assay is not widely > available. > > Radioimmunoassay — Radioimmunoassays for cortisol use polyclonal or > monoclonal antibodies that are raised to a cortisol analogue that has > been conjugated to a protein carrier. Each antibody is characterized > in terms of its affinity and crossreactivity with other endogenous or > exogenous steroids found in serum. Antibody, labeled cortisol tracer, > and cortisol standard are used to perform the assay. The results are > dependent upon the specificity of the antibody used in the assay. Both > liquid-phase and solid-phase assays of requisite sensitivity and > specificity are widely available in reference laboratories and in kit > form. Serum total cortisol is measured. > > Other immunoassays — Variations on radioimmunoassays using > fluorescent, chemiluminescent, and other labels in place of > radioisotopic labels, and two-site antibody designs (one antibody is > bound to a solid substrate, the other carries the radioactive or other > label, and the steroid forms a bridge between them) have similar > sensitivity and specificity and are available for use in automated > analyzers. The results, like those of radioimmunoassay, are dependent > upon the specificity of the antibody used in the assay. > > Structurally based assays — In contrast to antibody-based assays, > structurally based assays (HPLC, mass spectrometry) are highly > specific for the cortisol molecule; they also can measure synthetic > steroids [6] . The development of high-throughput techniques to > simultaneously measure multiple samples makes these labor-intense > assays feasible for commercial use [7] . This method separates > cortisol from other steroids and steroid metabolites; cortisol is then > measured fluorometrically or spectrophotometrically [8] . > > Normal values — The serum cortisol concentration normally reflects > that of corticotropin (ACTH) and therefore has circadian rhythmicity > (show figure 1 and show figure 2). Normal values vary with the > particular assay. The following values are representative of an > average radioimmunoassay; those obtained by competitive protein > binding assay would be similar, and fluorometric assay results are > about 3 µg/dL (85 nmol/L) higher [9] . > > In normal subjects serum cortisol concentrations are higher in the > early morning (about 6 AM), ranging from 10 to 20 µg/dL (275 to 555 > nmol/L). Serum cortisol concentrations range from 3 to 10 µg/dL (85 to > 275 nmol/L) at 4 PM, and the concentrations are lowest, less than 5 > µg/dL (140 nmol/L), one hour after the usual time of sleep (show > figure 2). > > Interpretation — Cortisol secretion is episodic and the normal ranges > are broad. A single serum value, if it falls within the normal range, > is inconclusive. An individual can have partial pituitary or adrenal > insufficiency but maintain plasma ACTH and serum cortisol > concentrations within their respective normal ranges. For these > reasons, stimulation or suppression testing should be performed when > there is doubt. Nevertheless, samples drawn at the appropriate time > for the suspected endocrine dysfunction can be very helpful in > excluding adrenal hypofunction or hyperfunction. > > Patients with primary or secondary adrenal insufficiency have low > early morning serum cortisol concentrations. If the value is greater > than 10 µg/dL (276 nmol/L), it is unlikely that the patient has > clinically important adrenal insufficiency, whereas if it is less than > 3 µg/dL (83 nmol/L), the probability of adrenal insufficiency is high. > (See " Diagnosis of adrenal insufficiency in adults " ). Since serum > cortisol is often undetectable one hour after the beginning of sleep, > measurement at this time does not identify patients with adrenal > insufficiency. > Patients with congenital adrenal hyperplasia may have normal or low > serum cortisol values (corresponding to simple virilizing and > " late-onset " CYP21A2 deficiency types) in the early morning. > Most patients with Cushing's syndrome have early morning serum > cortisol concentrations within or slightly above the normal range. In > contrast, serum cortisol concentrations one hour after sleep are > almost always high (greater than 7.5 µg/dL [207 nmol]) and are often > equal to the early morning values (ie, they have an abnormal or absent > circadian rhythm) [10] . (See " Establishing the diagnosis of Cushing's > syndrome " ). > Important caveats — Cortisol secretion normally reflects ACTH > secretion. As a result, the same caveats concerning circadian > rhythmicity, stress, and glucocorticoid administration also pertain to > it, except that recent hydrocortisone (cortisol) or cortisone > administration may result in high serum cortisol concentrations. The > longer disappearance half-time of cortisol than of ACTH (about 80 > versus eight minutes) and the several minute lag in its secretion > after ACTH stimulation tend to damp excursions in serum cortisol > relative to those of ACTH. > > Several other factors must be considered in interpreting serum > cortisol results. > > CBG — Serum cortisol concentrations do not correlate well with > cortisol production rates unless the CBG concentration is accounted > for [11] . Hepatic CBG synthesis is increased by estrogens [12-14] , > and early morning serum total cortisol concentrations of 50 µg/dL > (1400 nmol/L) or higher are not unusual during pregnancy or high dose > oral contraceptive use [15,16] . Cortisol dissociates rapidly from > CBG, so that early morning values are usually normal in these women. > Insulin and insulin-like growth factor-1 inhibit CBG secretion in > vitro, and serum CBG concentrations inversely correlated with indexes > of insulin secretion such as fasting serum glucose concentrations and > A1C are values [17] . Serum CBG concentration is increased in obese > patients who have glucose intolerance. Some individuals have low > levels of CBG on a genetic basis. > > Hepatic and renal dysfunction — Even relatively severe hepatic > dysfunction has little effect on serum cortisol concentrations [18] . > Renal failure also has little effect on them, although retained > cortisol metabolites may interfere in some radioimmunoassays [19] . > > Thyroid hormone — Thyroid hormone regulates the rate of cortisol > metabolism, but hypothalamic-pituitary feedback mechanisms are intact > and serum cortisol concentrations are within normal limits in patients > with hypothyroidism or hyperthyroidism. > > Body weight — Body weight has no appreciable effect on serum cortisol > concentrations, but severe malnutrition apparently has a greater > inhibitory effect on cortisol metabolism than on cortisol production, > increasing serum cortisol concentrations slightly [20] . > > Age — It requires one year or more for infants to establish an adult > sleep-wake cycle, entrain their circadian rhythms, and establish an > adult pattern of ACTH and cortisol secretion [21] . Except for these > changes in infants and the fact that, for the first several days of > life, normal infants produce more cortisone than cortisol and have low > serum cortisol concentrations [22] , age has no effect on serum > cortisol concentrations. > > Depression — Major depressive disorders, especially severe melancholic > depression, can result in cortisol dynamics similar to those of > Cushing's disease [23-25] . However, most ambulatory patients with > major depression have normal hour-of-sleep serum cortisol concentrations. > > Synthetic glucocorticoids — Exogenously administered glucocorticoids > can alter serum cortisol values either directly, if they cross-react > with an antibody, leading to spurious elevations, or indirectly, if > they suppress the hypothalamic-pituitary-adrenal axis, leading to low > values. (See " Diagnosis of adrenal insufficiency in adults " ). > > Cross-reactivity depends upon the specificity of the antibody for > cortisol. This possibility is evaluated during the development of > antibody-based commercial assays and the results are available in the > assay kit instructions, or from the company. > > In contrast to antibody-based assays, structurally based assays (HPLC, > mass spectrometry) are highly specific for the cortisol molecule; they > also can measure synthetic steroids [6] . The development of > high-throughput techniques to simultaneously measure multiple samples > makes these labor-intense assays feasible for commercial use [7] . > Such assays are useful to evaluate surreptitious ingestion of > synthetic steroids or potential cross-reaction in an antibody-based assay. > > Depending upon the dose and duration of exogenous glucocorticoid > administration, serum cortisol values may also be suppressed, > reflecting secondary adrenal insufficiency. If this is the case, > medications should be tapered rather than stopped for testing. (See > " Glucocorticoid withdrawal " ). > > Non-glucocorticoid drugs — Several drugs induce hepatic cytochrome > P-450 enzymes that metabolize steroids. Barbiturates, phenytoin, > rifampin, aminoglutethimide, and mitotane increase the metabolic > clearance of steroids and of metyrapone. They have a preferential > effect on synthetic 9-fluoro steroids (eg, dexamethasone and > fludrocortisone) as compared with natural steroids. > > These drugs do not alter serum cortisol concentrations in normal > subjects, but they can interfere with dexamethasone suppression and > metyrapone stimulation tests and necessitate increased steroid > replacement dosage in patients with adrenal insufficiency. > > Alcohol abuse — Alcohol abuse sufficient to increase serum hepatic > enzyme concentrations, especially gamma-glutamyltransferase, can cause > pseudo-Cushing's syndrome and high serum cortisol concentrations [26] . > > Sepsis — Patients with severe illness and sepsis have reduced CBG and > albumin levels that result in lower serum cortisol levels [27,28] . > > SERUM FREE CORTISOL — The biologically active fraction of cortisol in > serum is free cortisol. Although a variety of methods have been > developed for measuring serum free cortisol [5,29-32] , they are > technically demanding and expensive and are not in general use. > However, recent reports of decreased total cortisol levels in sepsis > and critical illness have led to increased interest in measurement or > calculation of free cortisol levels in measurement or calculation of > free cortisol levels in these patients [27,28,33] . (See " Evaluation > of the response to ACTH in adrenal insufficiency " , section on Critical > illness). > > CORTISOL PRECURSORS — Several biosynthetic precursors of cortisol, > including pregnenolone, 17-hydroxypregnenolone, progesterone, > 17-hydroxyprogesterone, and 11-deoxycortisol, can be measured by > radioimmunoassay directly or after solvent partition and/or > chromatography [30,34] . > > Normal values — The normal values for these compounds are as follows: > > Serum 11-deoxycortisol is undetectable in normal subjects by current > assays (ie, <1 µg/dL or 30 nmol/L at 8 AM). > The early morning serum 17-hydroxyprogesterone concentration ranges > from 60 to 300 ng/dL (1.8 to 19 nmol/L60 to 300 ng/dL) in men, 20 to > 100 ng/dL (0.6 to 3 nmol/L) in women during the follicular phase of > the menstrual cycle, 50 to 350 ng/dL (1.5 to 10.6 nmol/L) during the > luteal phase, and 600 ng/dL (18 nmol/L) and more by the end of pregnancy. > Interpretation — These assays are not commonly used for assessment of > hypothalamic-pituitary-adrenal function, but some of them do have > specific applications. > > Serum 17-hydroxyprogesterone can be measured before and after > administration of cosyntropin (ACTH) in patients expected to have the > 21-hydroxylase (P-450c21) deficiency variant of congenital adrenal > hyperplasia [35,36] . Return of the early morning serum > 17-hydroxypregnenolone or 17-hydroxyprogesterone concentration to > normal can be used as an index of the adequacy of treatment in this > disorder [37] . > Serum 11-deoxycortisol can be measured in tests of pituitary ACTH > secretory reserve using metyrapone [38] . (See " Metyrapone stimulation > tests " ). > One or more of these cortisol precursors may be increased in the serum > of patients with adrenal carcinoma [39] . > > MEASUREMENT OF SALIVARY CORTISOL CONCENTRATION — Serum free cortisol > diffuses freely into saliva. Therefore, measurements of salivary > cortisol more accurately reflect serum free cortisol concentrations > than do measurements of serum total cortisol. The salivary cortisol > concentration is independent of salivary flow rate [40,41] . > > Assay — Saliva (2.5 mL) is obtained after rinsing the mouth but before > brushing the teeth, either by unstimulated flow or after chewing > uncoated gum or a cotton tube (Plain Salivette, Sarstedt, Newton, NC), > and can be stored at room temperature for many days [42] or frozen for > extended periods. The sample is thawed, centrifuged at 1500 x g for 10 > min at 4ºC, and 2 mL of the supernatant is added to 10 mL of > dichloromethane [43] . The dichloromethane is aspirated and > evaporated, and the dried extract is reconstituted in assay buffer and > assayed by competitive protein-binding assay [2,44] , radioimmunoassay > [44,45] , or enzyme immunoassay [46] . Radioimmunoassay of unextracted > saliva has also been described [47,48] . > > With the development of high-affinity antisera that react specifically > with the D ring of cortisol, sensitivity has been improved, and > interference by other steroids has been minimized. > > Normal values — Salivary cortisol concentrations vary diurnally, with > concentration of about 5.6 ng/mL (15.4 nmol/L) at 8 to 9 AM and about > 1 ng/mL (2.8 nmol/L) at 11 PM [43,45,48] (show table 1). The values in > obese men and women are similar [43] . Additional work is needed to > evaluate the late night normal range in older patients with medical > illness [49] . > > Interpretation — Morning salivary cortisol concentrations are > decreased in adrenal insufficiency, while late evening salivary > cortisol concentrations are increased in Cushing's syndrome. Both the > competitive protein-binding assay and cortisol radioimmunoassays > crossreact with other steroids. The competitive protein-binding assay > crossreacts with 17-hydroxyprogesterone and 11-deoxycortisol, for > example; as a result, cortisol values may be artifactually increased > in patients with congenital adrenal hyperplasia and adrenal carcinoma > or after metyrapone administration. Some radioimmunoassays are more > specific. Cortisol can be chromatographically separated from other > steroids before assay in these situations [43] . > > More recently, developments of liquid chromatography mass spectrometry > methods with less cross-reactivity than antibody-based methods, may > yield fewer false positive results when used for the diagnosis of > Cushing's syndrome [50] . > > Measuring salivary cortisol is especially useful in assessing cortisol > secretion serially in ambulatory patients, who can collect multiple > samples and store them in a refrigerator or freezer or even at room > temperature for several days between clinic visits. They are also > helpful in the evaluation of patients suspected of having cyclical > Cushing's syndrome [45,51-54] . (See " Establishing the diagnosis of > Cushing's syndrome " ). > > SUMMARY > > Measurement of total, free, and salivary cortisol has been advocated > for the assessment of adrenal function. The results are affected by > the following factors: > > The assay methodology affects the normal range. Currently available > antibody-based assays cross react with non-cortisol steroids and have > a higher upper limit of normal than structurally-based assays such as > high pressure liquid chromatography. > Changes in CBG and albumin, the binding proteins for cortisol, affect > total serum levels, but not free levels in the serum or saliva. These > proteins may be substantially reduced in critically ill patients, so > that total cortisol values may not reflect adrenal function. > Conversely, estrogen-induced increases in CBG may mask low cortisol > production. > In individuals with normal sleep-wake cycles, cortisol values are > lowest around bedtime, and peak in the early morning. This physiologic > difference has been used for diagnostic purposes: > > Patients with Cushing's syndrome have elevated late night salivary and > serum cortisol values. (See " Establishing the diagnosis of Cushing's > syndrome " ). > Patients with severe adrenal insufficiency may have low early morning > serum cortisol concentrations. If the value is greater than 10 µg/dL > (276 nmol/L), it is unlikely that the patient has clinically important > adrenal insufficiency, whereas if it is less than 3 µg/dL (83 nmol/L), > the probability of adrenal insufficiency is high. > Use of UpToDate is subject to the Subscription and License Agreement . > > REFERENCES > > 1 , DH, s, LT. A method for the determination of > 17-hydroxycorticosteroids in blood; 17-hydroxycorticosterone in the > peripheral circulation. J Clin Endocrinol Metab 1952; 12:519. > 2 , BE. Some studies of the protein-binding of steroids and > their application to the routine micro and ultramicro measurement of > various steroids in body fluids by competitive protein-binding > radioassay. J Clin Endocrinol Metab 1967; 27:973. > 3 , BEP. Non-chromatographic radiotransinassay for cortisol: > Application to human adult serum, umbilical cord serum, and amniotic > fluid. J Clin Endocrinol Metab 1975; 41:1050. > 4 MATTINGLY, D. A simple fluorimetric method for the estimation of > free 11-hydroxycorticoids in human plasma. J Clin Pathol 1962; 15:374. > 5 Ballard, PL, , JP, Graham, BS, Baxter, JD. A radioreceptor > assay for evaluation of the plasma glucocorticoid activity of natural > and synthetic steroids in man. J Clin Endocrinol Metab 1975; 41:290. > 6 Guo, T, , RL, Singh, RJ, Soldin, SJ. Simultaneous > determination of 12 steroids by isotope dilution liquid > chromatography-photospray ionization tandem mass spectrometry. Clin > Chim Acta 2006; 372:76. > 7 , RL, Grebe, SK, Singh, RJ. Quantitative, highly sensitive > liquid chromatography-tandem mass spectrometry method for detection of > synthetic corticosteroids. Clin Chem 2004; 50:2345. > 8 Gotelli, GR, Wall, JH, Kabra, PM, Marton, LJ. Fluorometric > liquid-chromatographic determination of serum cortisol. Clin Chem > 1981; 27:441. > 9 Gore, M, Lester, E. Comparison of a fluorimetric method and a > competitive protein binding assay kit for the determination of plasma > hydroxycorticosteroids. Ann Clin Biochem 1975; 12:160. > 10 Papanicolaou, DA, Yanovski, JA, Cutler, GB Jr, et al. A single > midnight serum cortisol measurement distinguishes Cushing's syndrome > from pseudo-Cushing states. J Clin Endocrinol Metab 1998; 83:1163. > 11 Bright, GM, Darmaun, D. Corticosteroid-binding globulin modulates > cortisol concentration responses to a given production rate. J Clin > Endocrinol Metab 1995; 80:764. > 12 Brien, TG. Human corticosteroid binding globulin. Clin Endocrinol > 1981; 14:193. > 13 Coolens, JL, Van Baelen, H, Heyns, W. Clinical use of unbound > plasma cortisol as calculated from total cortisol and > corticosteroid-binding globulin. J Steroid Biochem 1987; 26:197. > 14 Musa, BU, Seal, US, Doe, RP. Elevation of certain plasma proteins > in man following estrogen administration: A dose-response > relationship. J Clin Endocrinol Metab 1965; 25:1163. > 15 , RE, Nokes, LA, Chen Jr, PS, Black, RL. Estrogens and > adrenocortical function in man. J Clin Endocrinol Metab 1960; 20:495. > 16 Aron, DC, Tyrrell, JB, Fitzgerald, PA, et al. Cushing's syndrome: > Problems in diagnosis. Medicine 1981; 60:25. > 17 Fernández-Real, JM, Grasa, M, Casamitjana, R, et al. Plasma total > and glycosylated corticosteroid-binding globulin levels are associated > with insulin secretion. J Clin Endocrinol Metab 1999; 84:3192. > 18 McCann, VJ, Fulton, TT. Cortisol metabolism in chronic liver > disease. J Clin Endocrinol Metab 1975; 40:1038. > 19 , G, Gomez-, C, Meikle, AW, Jubiz, W. Evaluation of > the hypothalamic hypophyseal adrenal axis in patients receiving > long-term hemodialysis. Arch Intern Med 1982; 142:1448. > 20 , SR, Bledsoe, T, Chhetri, MK. Cortisol metabolism and the > pituitary-adrenal axis in adults with protein-calorie malnutrition. J > Clin Endocrinol Metab 1975; 40:43. > 21 s, R.C. Diurnal variation of plasma 17- hydroxycorticosteroids > in children. J Clin Endocrinol Metab 1967; 27:75. > 22 HILLMAN, DA, GIROUD, CJ. PLASMA CORTISONE AND CORTISOL LEVELS AT > BIRTH AND DURING THE NEONATAL PERIOD. J Clin Endocrinol Metab 1965; > 25:243. > 23 Pfohl, B, Sherman, B, Schlechte, J, Stone, B. Pituitary- adrenal > axis rhythm disturbances in psychiatric depression. Arch Gen > Psychiatry 1985; 42:897. > 24 Pfohl, B, Sherman, B, Schlechte, J, Winokur, G. Differences in > plasma ACTH and cortisol between depressed patients and normal > controls. Biol Psychiatry 1985; 20:1055. > 25 Schlechte, JA, Coffman, T. Plasma free cortisol in depressive > illness — a review of findings and clinical implications. Psychiatr > Med 1985; 3:23. > 26 Fink, RS, Short, F, Marjot, DH, , VHT. Abnormal suppression of > plasma cortisol during the intravenous infusion of dexamethasone to > alcoholic patients. Clin Endocrinol 1981; 15:97. > 27 Ho, JT, Al-Musalhi, H, Chapman, MJ, et al. Septic shock and sepsis: > a comparison of total and free plasma cortisol levels. J Clin > Endocrinol Metab 2006; 91:105. > 28 Hamrahian, AH, Oseni, TS, Arafah, BM. Measurements of serum free > cortisol in critically ill patients. N Engl J Med 2004; 350:1629. > 29 Migeon, CJ, Lawrence, B, Bertrand, J, Holman, GH. In vivo > distribution of some 17-hydroxycorticoids between the plasma and red > blood cells of man. J Clin Endocrinol Metab 1959; 19:1411. > 30 Newsome, HH Jr, Clements, AS, Borum, EH. The simultaneous assay of > cortisol, corticosterone, 11-deoxycortisol, and cortisone in human > plasma. J Clin Endocrinol Metab 1972; 34:473. > 31 Robin, P, Predine, J, Milgrom, E. Assay of unbound cortisol in > plasma. J Clin Endocrinol Metab 1977; 46:277. > 32 Huang, W, Kalhorn, TF, Baillie, M, et al. Determination of free and > total cortisol in plasma and urine by liquid chromatography-tandem > mass spectrometry. Ther Drug Monit 2007; 29:215. > 33 Arafah, BM, Nishiyama, FJ, Tlaygeh, H, Hejal, R. Measurement of > salivary cortisol concentration in the assessment of adrenal function > in critically ill subjects: a surrogate marker of the circulating free > cortisol. J Clin Endocrinol Metab 2007; 92:2965. > 34 , DC, Hopper, BR, Lasley, BL, et al. A simple method for > the assay of eight steroids in small volumes of plasma. Steroids 1976; > 28:179. > 35 New, MI, Lorenzen, F, Lerner, AJ, et al. Genotyping steroid > 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol > Metab 1983; 57:320. > 36 White, PC, New, MI, Dupont, B. Congenital adrenal hyperplasia. N > Engl J Med 1987; 316:1519. > 37 McKenna, TJ, , G, Orth, DN, et al. The biosynthesis of > androgens in 21-hydroxylase deficiency. In: Adrenal Androgens, > Genazzani, AR, et al (Eds), Raven Press, New York 1980. p.135. > 38 Meikle, AW, West, SC, Weed, JA, Tyler, FH. Single dose metyrapone > test: 11-beta-hydroxylase inhibition by metyrapone and reduced > metyrapone assayed by radioimmunoassay. J Clin Endocrinol Metab 1975; > 40:290. > 39 Bertagna, C, Orth, DN. Clinical and laboratory findings and results > of therapy in 58 patients with adrenocortical tumors admitted to a > single medical center (1951 to 1978). Am J Med 1981; 71:855. > 40 , RF, Riad-Fahmy, D, Read, GF. Adrenal status assessed by > direct radioimmunoassay of cortisol in whole saliva or parotid saliva. > Clin Chem 1978; 24:1460. > 41 Umeda, T, Hiramatsu, R, Iwaoka, T, et al. Use of saliva for > monitoring unbound free cortisol levels in serum. Clin Chim Acta 1981; > 110:245. > 42 Chen, YM, Cintron, NM, Whitson, PA. Long-term storage of salivary > cortisol samples at room temperature. Clin Chem 1992; 38:304. > 43 Laudat, MH, Cerdas, S, Fournier, C, et al. Salivary cortisol > measurement: A practical approach to assess pituitary-adrenal > function. J Clin Endocrinol Metab 1988; 66:343. > 44 Allolio, B, Hoffmann, J, Linton, EA, et al. Diurnal salivary > cortisol patterns during pregnancy and after delivery: Relationship to > plasma corticotropin-releasing-hormone. Clin Endocrinol 1990; 33:279. > 45 Raff, H, Raff, JL, Findling, JW. Late-night salivary cortisol as a > screening test for Cushing's syndrome. J Clin Endocrinol Metab 1998; > 83:2681. > 46 Raff, H, Homar PJ, Burns EA. Comparison of two methods for > measuring salivary cortisol. Clin Chem 2002; 48:207. > 47 Viera, JG, Noguti KO, Hidal, JT, et al. Measurement of saliva > cortisol as a method for the evaluation of free serum fraction. Arq > Bras Endocrinol Metab 1984; 28:8. > 48 Castro, M, Elias, PC, Quidute, AR, et al. Out-patient screening for > Cushing's syndrome: the sensitivity of the combination of circadian > rhythm and overnight dexamethasone suppression salivary cortisol > tests. J Clin Endocrinol Metab 1999; 84:878. > 49 Liu, H, Bravata, DM, Cabaccan, J. Elevated late-night salivary > cortisol levels in elderly male type 2 diabetic veterans. Clin > Endocrinol (Oxf) 2005; 63:642. > 50 Baid, SK, Sinaii, N, Wade, M, et al. Radioimmunoassay and tandem > mass spectrometry measurement of bedtime salivary cortisol levels: a > comparison of assays to establish hypercortisolism. J Clin Endocrinol > Metab 2007; 92:3102. > 51 , PJ, s, JR, Dyas, J, et al. Salivary cortisol levels in > true and apparent hypercortisolism. Clin Endocrinol 1984; 20:709. > 52 Hermus, AR, Pieters, GF, Borm, GF, et al. Unpredictable > hypersecretion of cortisol in Cushing's disease: Detection by daily > salivary cortisol measurements. Acta Endocrinol (Copenh) 1993; 128:428. > 53 Mosnier-Pudar, H, Thomopoulos, P, Bertagna, X, et al. Long- distance > and long-term follow-up of a patient with intermittent Cushing's > disease by salivary cortisol measurements. Eur J Endocrinol 1995; 133:313. > 54 Papanicolaou, DA, Mullen, N, Kyrou, I, Nieman, LK. Nighttime > salivary cortisol: a useful test for the diagnosis of Cushing's > syndrome. J Clin Endocrinol Metab 2002; 87:4515. > > ©2009 UpToDate® • customerservice@... > Quote Link to comment Share on other sites More sharing options...
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