text stringlengths 16 2.35k | tokenCount int64 5 450 | pageStart int64 1 43 | pageEnd int64 1 43 | hash stringlengths 64 64 |
|---|---|---|---|---|
Although there are no formal controlled studies of conse- quences of cure in pediatric Cushing’s syndrome, improvements in growth and body composition after treatment are reported in both patients with adrenal and those with pituitary causes (24, 25). | 52 | 4 | 4 | 523524dff8c086d4b25f02ef65826688687f8f1951d1f7e985f85c37e0568f24 |
Final stature in patients with endogenous Cushing’s syn- drome was reported to be disappointing (26), but more recent data showed that most patients reach a final height within their predicted parental target range (24). | 44 | 4 | 4 | cd2fe6a4b5ab8c0df6d2dca449a649393ed07eddcc602d4c64383812fb996cba |
Treatment of patients with moderate to severe Cushing’s syn- drome clearly reduces mortality and morbidity. Because Cush- ing’s syndrome tends to progress and severe hypercortisolism is probably associated with a worse outcome, it is likely that early recognition and treatment of mild disease would reduce the risk ofre... | 90 | 4 | 4 | 734238c364758a94ee36a40ffff46a70adf2491fbf61312d5b725f08728103e6 |
OurrecommendationsfortestingforCushing’ssyndromeare based on direct evidence from observational studies indicating a large treatment effect (which we have rated as low to moderate quality evidence) on morbidity and mortality in patients diag- nosed with the condition. | 56 | 4 | 4 | 919c6772fcb57ac5ed8d59a3b3a127350be5e9ac330abd10a31bdfa7bb971ffb |
The next section of this document focuses on evidence that bears indirectly on these recommenda- tions. The research in this area yields data on the likelihood of Cushing’s syndrome in certain populations and on the accuracy of currently available tests in these populations. | 52 | 4 | 4 | 5bd6c859a2b95030089f380ee7d12b5b7243343eb7525c81ca339aeb84a2721b |
As a result, the majority of our recommendations are based on very low- to low-quality evidence. Higher-quality evidence to support testing should come from studies directly comparing the effect of testing strategies on patient-important outcomes. | 45 | 4 | 4 | 4a0f6995e9bd8603d9b93186cbc4c01a2136e6a590fa18984aa36e643bf995b9 |
To date such evidence is not available in this field. These guidelines focus on the more common clinical scenar- ios, with brief mention of conditions and situations that are rare or more complicated than space limitations allow; we hope that the reader will investigate these further. | 53 | 4 | 4 | 16f151a079033501ce6cd98d1e58bc94e65a4e6d144ba57cc456e43bc1ad5ba7 |
3.0 Diagnosis of Cushing’s syndrome Who should be tested 3.1Werecommendobtainingathoroughdrughistorytoexclude exogenous glucocorticoid exposure leading to iatrogenic Cush- ing’s syndrome before conducting biochemical testing (1 QQQQ ). | 67 | 4 | 4 | e2026bea096b86114ece2b6374c884de736148b044dcfdf41a844207b7a8818b |
3.2 We recommend testing for Cushing’s syndrome in the fol- lowing groups: • Patients with unusual features for age ( e.g. osteoporosis, hypertension) (Table 1) (1 QQEE ) • Patientswithmultipleandprogressivefeatures,particularly those that are more predictive of Cushing’s syndrome (Ta- ble 1) (1 QQEE ) • Children with ... | 117 | 4 | 4 | 3308ccfdd4504de20abf7f34b3a6e3ca44b9afdd79a675d06deb33201a8f6087 |
3.3 We recommend against widespread testing for Cushing’s syndrome in any other patient group (1 QEEE ). 3.1 Evidence Features of Cushing’s syndrome may occur as a result of exog- enousglucocorticoiduse.TheseverityoftheCushingoidfeatures TABLE 2. | 68 | 4 | 4 | 481d64c3d5700eb63bfa96855ce63badabed7450ad6a8cd8c9bbc793801a93a2 |
Conditions associated with hypercortisolism in the absence of Cushing’s syndrome a Conditions Some clinical features of Cushing’s syndrome may be present Pregnancy Depression and other psychiatric conditions Alcohol dependence Glucocorticoid resistance Morbid obesity Poorly controlled diabetes mellitus Unlikely to have... | 133 | 4 | 4 | 88fb6fbecba8a8bbe18496fd26cce1ad60d657c5da00249ec93a4a2d9c2e01ce |
If there is a high clinical index of suspicion, the patient should undergo testing, particularly those within the first group. J Clin Endocrinol Metab, May 2008, 93(5):1526–1540 jcem.endojournals.org 1529 Downloaded from https://academic.oup.com/jcem/article/93/5/1526/2598096 by University of Wisconsin System user on 2... | 93 | 4 | 4 | 35baa0b845171cf48ffa67d54ffcc7aaaef05cab83fbb5b4face30c7e136ea41 |
depends on the potency of the preparation used, its dose, the route and duration of its administration, and whether concom- itant medications prolong its half-life (27). A thorough drug his- tory noting current or recent use of these medications, oral, rec- tal, inhaled, topical, or injected, should be obtained before ... | 80 | 5 | 5 | 3c62b165c23cd435710d8042662869ec5e09c3e3b3834254a485c2ba621730c9 |
In particular, glu- cocorticoid components of skin creams (including bleaching agents), herbal medications, “tonics,” and joint or nerve injec- tions may be overlooked. | 44 | 5 | 5 | b3ce548f258243889af0a4a18d3d58f056b948fdfc6b012038aadcffdd61bd17 |
Megestrol acetate (medroxyprogester- one acetate) is a synthetic progesterone derivative that has glu- cocorticoid activity and in high doses may cause Cushing’s syndrome (29). | 48 | 5 | 5 | 78d39fb93fe5b720050ddbb90e2e193a2d090ff6a64d0b46a435c7c5b9062f9b |
Our recommendation is based on high-quality evidence because it derives from the common observation that pursuing the alternative, testing to establish the diagnosis of Cushing’s syndrome without first excluding exogenous glu- cocorticoiduse,isassociatedwithaverylargeriskofundesirable effects (including unnecessary tes... | 77 | 5 | 5 | 9f3b423223899c0d551dac869739104a80f370024127f078b3159d01cbcbcb41 |
3.2 Evidence Cushing’s syndrome is more likely to be present when a large number of signs and symptoms, especially those with high dis- criminatory index ( e.g. myopathy, plethora, red striae, easy bruising, and thin skin in the young) are present (6, 8). | 65 | 5 | 5 | 186f4fb9f663fad090e42b0c1da97fd4629f14c2328ec34a0e68f271f6cc1d52 |
However, there is a wide spectrum of clinical manifestations at any given level of hypercortisolism. Because Cushing’s syndrome tends to progress, accumulation of new features increases the probability that the syndrome is present. | 45 | 5 | 5 | d38af38c5407354ffbedeaaab17123bedb99595cdbc502b37c9c5fa3524a5bc8 |
A review of old photographs of the patient may help the clinician better appreciate whether physical changes have occurred over time. In children, the sensitivity of combined reduced linear growth and increased weight is quite high. | 40 | 5 | 5 | 4d6e311a2459b05fbe584859a17ef6c7ce703c9883eee6597a96ffad034af281 |
Although the probability of Cushing’s syndrome has not been evaluated in a large number of children, clinical experience suggests that the specificity of these clinical features for the diagnosis is also very high (30). | 41 | 5 | 5 | a2c87f3ead1200975f031e49c2e34b546a0778cc2e010bafdb0627b2e83b6db8 |
As a result, tests for Cushing’s syndrome are not indicated in obese children unless their statural growth rate has slowed. Clinicians often evaluate patients with an incidentally found adrenal nodule for autonomous adrenal cortisol excess. | 47 | 5 | 5 | 3f6357ee8d9e7218ae61977563a8b7ed4f635f2f1b503f62c217c2144cd3ed54 |
Such patients usually do not present with overt clinical features of Cushing’s syndrome, but biochemical hypercortisolism is presentinalargefraction(upto10%).Bulow etal. | 41 | 5 | 5 | bf66073aa30c19b8214eb3f5d6c8c7645aa588925e0951f917b1a7ef74f97ef8 |
(31)reported 2% prevalence of Cushing’s syndrome; Libe et al. (32) reported 18%; Terzolo et al. (21) quoted 5–20%, depending on referral bias and diagnostic tests and criteria. | 50 | 5 | 5 | b78b46268e7c967ea47c0b31944cc22cf7c5653bbb0178ece5f3fd3609b06027 |
3.3 Evidence Testing for Cushing’s syndrome in certain high-risk populations has shown an unexpectedly high incidence of unrecognized Cushing’s syndrome as compared with the general population. | 40 | 5 | 5 | 53b3d37f4b333c06ba676ace33ea8a2194cd73f55c1cf0f1514c7c2ef55d4661 |
Although there are limited data on the prevalence of the syn- drome in these disorders, the diagnosis should be considered. In one study, 2–3.3% of patients with poorly controlled di- abetes mellitus had surgically confirmed Cushing’s syndrome or mild hypercortisolism. | 64 | 5 | 5 | a224eb4d0f2b79eb7051589e631cbb15504853dc9f5583d20bfe2b5e6a720abe |
Most of these patients had unilateral ad- renal adenomas (33). In another recent report, one of 99 patients with newly diagnosed diabetes mellitus had surgically proven Cushing’s disease (34). | 43 | 5 | 5 | af920b22bc4498414fb5597d5ec524719eda69a88408a8e25c11ae962245cf59 |
Another study of 86 consecutive obese subjects referred to an endocrine clinic with diabetes mellitus, hypertension, and/or the polycystic ovary syndrome found a 5.8% incidence of Cushing’s syndrome (35). | 47 | 5 | 5 | 800e905f192fd156837e823c9f98823b6ead15a729b840ae610ebec13e73c1ca |
Screening studies of patients with hypertension reported a 0.5–1% prevalence of Cushing’s syndrome (36, 37). Unsus- pected Cushing’s syndrome also was found in as many as 10.8% of older patients with osteoporosis and vertebral fracture in whom comprehensive testing was done for secondary causes (38). | 75 | 5 | 5 | 707027750c5e056ba124f39c2f701e7fdd5ebd06e39a79a01d4a06e421c19d0e |
Unfortunately, there is little information on additional co- morbidities and risk factors in these studies. The few data on the outcome, after surgical remission of hy- percortisolism, in patients with unsuspected Cushing’s syn- drome are mixed; hypertension and diabetes did not improve in all individuals (20–23). | 69 | 5 | 5 | 593a46c39a3c252c98032aa8982355a3fb9c4ad0a75df2c3b30f34bf55cfd0e5 |
Patients with familial disease that puts them at risk of Cush- ing’s syndrome ( e.g. Carney complex, multiple endocrine neo- plasia-1) should be evaluated by an endocrinologist as part of a surveillance screening program. | 53 | 5 | 5 | 81af0342f5dea76979b60af9e1dfca793b990da123ecb43873ef64a7701876e2 |
3.3 Values Because of the rarity of Cushing’s syndrome, the high prevalence of conditions such as diabetes mellitus, obesity, and depression, andthelimitationsofthescreeningtests,theriskoffalse-positive test results is high. | 53 | 5 | 5 | 6cf202d51f0f041082ebf8461aa15333ad0a3536fbabb713139a0b6ebee5057e |
False-positive results, with their attendant costs, are reduced if case detection is limited to individuals with an increased pretest probability of having the disorder. The sub- sequent testing, labeling, and treatment may harm individuals with false-positive results and distract attention from the treat- ment of the ... | 64 | 5 | 5 | e1d5a0073ce6807fce241ae4dee1541580bd5799e246c119f906d07bf65a5d0d |
The proposed testing strategy places higher value on reducing the number of false-positive test results, particularly in patients with very mild disease in whom the benefits of intervention are unproven. Conversely, once the clinical scenario suggests a high pretest probability of the disorder, sensitivity needs to be ... | 63 | 5 | 5 | c5f4c3bf1a042c1541aa1f2e893118a484468bbc5af410cc4d720034e66b9c76 |
This approach also seeks to use more convenient and less expensive tests. Initial testing 3.4 For the initial testing for Cushing’s syndrome, we recom- mendoneofthefollowingtestsbasedonitssuitabilityforagiven patient (Fig. | 54 | 5 | 5 | f027f41a87e8df8bf51e4781c347a45d4a598cc66fd15cd9997b34d0c06c7625 |
1) (1 QEEE ): 3.4.1 UFC (at least two measurements) 3.4.2 Late-night salivary cortisol (two measurements) 3.4.3 1-mg overnight DST 3.4.4 Longer low-dose DST (2 mg/d for 48 h) 3.5 We recommend against the use of the following to test for Cushing’s syndrome (1 QEEE ): | 92 | 5 | 5 | 856b8e249178cd3af80b2bd507a8cbe0997c1b04db87c81b96e1b5a135db14dd |
• Random serum cortisol or plasma ACTH levels • Urinary 17-ketosteroids • Insulin tolerance test • Loperamide test • Tests designed to determine the cause of Cushing’s syn- drome ( e.g. | 49 | 5 | 5 | 9d7147562abaa28ae9ff580301b9bda686fddaa22feffe8e270dcd063a52941a |
pituitary and adrenal imaging, 8 mg DST). 3.6 In individuals with normal test results in whom the pretest probability is high (patients with clinical features suggestive of 1530 Nieman et al. | 45 | 5 | 5 | b42f90b86387d1142995feb9fd36292f6bd69010482d93676a2195a571d12182 |
Guidelines for the Diagnosis of Cushing’s Syndrome J Clin Endocrinol Metab, May 2008, 93(5):1526–1540 Downloaded from https://academic.oup.com/jcem/article/93/5/1526/2598096 by University of Wisconsin System user on 20 February 2026 | 72 | 5 | 5 | ff1fcbc856e62ff8dac438999f1d14b8790e11a636ff529706340a4bfea48f83 |
Cushing’s syndrome and adrenal incidentaloma or suspected cy- clic hypercortisolism), we recommend further evaluation by an endocrinologist to confirm or exclude the diagnosis (1 QEEE ). | 43 | 6 | 6 | 01c776a8be4d2c631f34ddba25cda60af7ec5f200fcf48ad09b5d0f46b965e5b |
3.7 In other individuals with normal test results (in whom Cush- ing’s syndrome is very unlikely), we suggest reevaluation in 6 months if signs or symptoms progress (2 QEEE ). | 43 | 6 | 6 | ece5bd5a3ac0db1628f4e6cbfc46280a200c133a96187d18fb646d514c492322 |
3.8 In individuals with at least one abnormal test result (for whom the results could be falsely positive or indicate Cushing’s syndrome), we recommend further evaluation by an endocrinol- ogist to confirm or exclude the diagnosis (1 QEEE ). | 54 | 6 | 6 | ffacfe937602f035dd98711f31be335935641dd22a2b5a7566a9a8bb648c9ed2 |
3.4 Evidence In this section, we first discuss the testing strategies and then provide evidence for and remarks about each of the recom- mended tests that can be used to identify patients with Cushing’s syndrome. | 46 | 6 | 6 | 39bcf5cb2dc87db674d82e7a17211f9cfee7b5c9cfba78ded88ee324ca525cd9 |
Nonendocrinologist clinicians may perform the initial eval- uation for Cushing’s syndrome (or refer to an endocrinologist). In this setting, the goal is to choose a test with a high sensitivity for the disorder; unfortunately, no test has optimally high spec- ificity, so that false-positive results may occur. | 70 | 6 | 6 | 1d513890bd7d6c1a7e357d2319cad810f57be7c5705f155ee9350744cd05d03a |
The four recom- mended tests have acceptable diagnostic accuracy when the sug- gested cutoff points are used (2, 30). If the initial testing results arenormal,assumingthatthereisnoreasontomistrusttheresult (see remarks below), then the patient is very unlikely to have Cushing’s syndrome. | 70 | 6 | 6 | 060a18d864c8003a323e90896ba56967750d13195398b7a0b3a167d7159fef62 |
Thus, the patient can be reassured and no further testing need be done; a recommen- dation to return in 6 months if symptoms progress ensures that evolving symptoms or new features will not be ignored. | 41 | 6 | 6 | 7b6a1732a951340f4e343de4cfde20a9bb1d8966f24a65ae3cb6ef649d7d0868 |
Inpatientswithahighpretestprobability of Cushing’s syndrome, to expedite diagno- sis, the physician may elect to perform two tests simultaneously. 3.4 Remarks for all tests Measurement of cortisol (urine, serum, or salivary) is the end point for each of the rec- ommended tests. | 77 | 6 | 6 | ce0473c20cfe8c1312a8631b960f1b606434ddc4aa024706a31df9cc188f9ae7 |
As with all hormone as- says, the physician must be aware that sev- eral collection and assay methods are available for the measurement of cortisol, and results for a single sample measured in various assays may be quite different (39). | 49 | 6 | 6 | aab9a29d90c29d16afe7c17d396adc4df0f084267692ee745dc543854c143866 |
Assays differ widely in their accuracy; re- sults near the cutoff value on a single mea- surement often can be explained by assay variability. In particular, the expected sali- vary and serum concentrations in these tests are close to the functional limit of detection of the assays. | 60 | 6 | 6 | a713fac5f44bc3f3ab6a453908fbcf36265459cce251e897757b7faa58140d69 |
Because precision deteriorates at these levels, assays should be chosen on the basis of their performance at this low range. Normal ranges vary substantially, de- pendingonthemethodused,soitisessential to interpret test results in the context of the appropriate normal range. | 53 | 6 | 6 | a3edf23cf47d25aa78b20cc13677e6f2b41cb7b94915744a07f3eda11c081a82 |
Antibody-based immunoassays such asunextractedRIAandELISAcanbeaffectedbycross-reactivity with cortisol metabolites and synthetic glucocorticoids. In con- trast, structurally based assays such as HPLC and tandem mass spectrometry (LC-MS/MS) do not pose this problem and are being used with increasing frequency. | 79 | 6 | 6 | a16088cc36eb62a32589756259325e99c909875da3bde9e512741e982eb7942a |
However, there are also drugs (carbamazepine and fenofibrate) that may interfere with someofthesechromatographicmethods(Table3),therebycaus- ing falsely elevated values (40, 41). | 49 | 6 | 6 | 20ddfb20ccdba73ac4f362dd41714fcc19ba8a3772cf7e9116fd05c9206a2eb9 |
Upper limits of normal are much lower with HPLC or LC-MS/MS than in antibody-based assays. For example, urine cortisol values obtained using HPLC may be as low as 40% of the value measured by RIA (42, 43). | 54 | 6 | 6 | f8a166277688dcedd747d349c4070b3114d118d13ccd2b0790434b0a2e304414 |
Estrogens increase the cortisol-binding globulin (CBG) con- centration in the circulation. Because serum assays measure total cortisol, false-positive rates for the overnight DST are seen in 50% of women taking the oral contraceptive pill (44). | 53 | 6 | 6 | b120871a05b498f6eadf5e5b58f2f59eed01df8d47cb930eb9137b8c5879f44f |
Wherever possible, estrogen-containing drugs should be withdrawn for 6 wkbeforetestingorretesting(45).Conversely,decreasesinCBG or albumin, which occur in the critically ill or nephrotic patient, are associated with decreased serum cortisol values (39, 46). | 61 | 6 | 6 | 99abfb8f3de4b99082ed47a3afeab95e168c6e18c341c9191dcb182efec132b3 |
Because the hypercortisolism of Cushing’s syndrome can be variable, we recommend that at least two measurements of urine or salivary cortisol be obtained. This strategy increases confi- denceinthetestresultsifconsistentlynormalorabnormalresults are obtained. | 59 | 6 | 6 | 8f75149c9c1dcbc93de130294d1b2ba6e2abc4ae1f96ef0411138b151308f728 |
Cushing’s syndrome suspected Perform one of the following tests ANY ABNORMAL RESULT Normal (CS unlikely) Consult endocrinologist Discrepant (Suggest additional evaluation) Normal (CS unlikely) ABNORMAL Cushing’s syndrome Exclude exogenous glucocorticoid exposure (consider endocrinologist consultation) 24-h UFC (> 2 tes... | 166 | 6 | 6 | 4dd61817a3e51aba08dc1313b4c02f5a41a016ed75a2e8787b2fe8983178b219 |
Algorithm for testing patients suspected of having Cushing’s syndrome (CS). All statements are recommendations except for those prefaced by suggest. Diagnostic criteria that suggest Cushing’s syndrome are UFC greater than the normal range for the assay, serum cortisol greater than 1.8 g/dl (50 nmol/liter) after 1 mg ... | 106 | 6 | 6 | 72473c186c8b76207b1097b4b296a306d50281bb9b3d5f8bacbf7f1f48fdecc2 |
J Clin Endocrinol Metab, May 2008, 93(5):1526–1540 jcem.endojournals.org 1531 Downloaded from https://academic.oup.com/jcem/article/93/5/1526/2598096 by University of Wisconsin System user on 20 February 2026 | 70 | 6 | 6 | bfff484a1b7e37b4915c41b57740b40a60fe87d93e65ef471a34ef831bce0f89 |
Remarks for dexamethasone tests Variable absorption and metabolism of dexamethasone may in- fluence the result of both the overnight 1-mg DST and the 48-h, 2 mg/d test. | 47 | 7 | 7 | c1340552f8ad7ba4f99bfe40c45e88f494c64a304da560145222283b7215a54c |
Drugs such as phenytoin, phenobarbitone, carbam- azepine, rifampicin, and alcohol induce hepatic enzymatic clear- ance of dexamethasone, mediated through CYP 3A4, thereby reducing the plasma dexamethasone concentrations (Table 3) (47). | 71 | 7 | 7 | 76291247c665752126ee13f68155ce21e76acae36ef533b905c92b65ee8ffcc6 |
Conversely, dexamethasone clearance may be reduced in patients with liver and/or renal failure. Dexamethasone levels show interindividual variation, however, even in healthy indi- viduals on no medication. | 49 | 7 | 7 | 974cc15d1da922a3ee52aa3acb85055d691862843ae32bf8d2d60aa62d941134 |
To evaluate for false-positive and negative responses, some experts have advocated simultaneous measurement of both cor- tisol and dexamethasone for these tests to ensure adequate plasma dexamethasone concentrations [ 5.6 nmol/liter (0.22 g/dl)] (48). | 64 | 7 | 7 | 2720a3f14e4971158b53426574850af3332df18bddd61ec2a403699092ec0869 |
However, given the limited availability outside the United States and cost of the dexamethasone assay, this other- wise desirable approach may not be feasible. As noted above, false-positive rates for the overnight DST are seen in 50% of women taking the oral contraceptive pill because of increased CBG levels (44). | 66 | 7 | 7 | e67de3dc799097f140beb7b81c9129eec8587fd61029df0ded00b2a2f524dd68 |
3.4.1 Evidence for use of UFC The introduction of UFC represented a major advance over mea- surement of 17-hydroxycorticosteroids (17OHCS), which re- flects both urine metabolites and cortisol. | 51 | 7 | 7 | 0e6548648cfdb423f3d660ac43aa8af621b8a72e1bd77decf27edf46182bf894 |
Because 17OHCS has high rates of false-positive and negative results, it is now rarely used. Since the 1970s, experts have advocated the use of UFC for making the diagnosis of Cushing’s syndrome (49, 50). | 49 | 7 | 7 | a1972389ee1ec7c9055dee059c56041dd0d5f73a1469625cdf7cebd0ecc1eb54 |
UFC pro- vides an integrated assessment of cortisol secretion over a 24-h period. It measures the cortisol that is not bound to CBG, which is filtered by the kidney unchanged. Therefore, unlike serum cortisol, which measures both CBG-bound and free hormone, UFC is not affected by conditions and medications that alter C... | 68 | 7 | 7 | 89e61a57418a8cf94f99979ccd48309a8fb12325c5c301b13be8aef7c3279a4b |
For example, healthy women taking oral estrogen may have increased CBG, and therefore high serum cortisol concen- tration, but their UFC remains normal. Because cortisol produc- tion is increased in Cushing’s syndrome, the amount of unbound hormone is higher, resulting in elevated UFC values. | 62 | 7 | 7 | a323b2c805ca99728540ceac73012f9f27af192d2b2bd864d8f8a900eef3b51b |
As with any other test, sensitivity and specificity of UFC are subject to the cutoffs selected. When the assay upper limit of normal is used as a criterion, the overall evidence supports the diagnostic accuracy of UFC in adults suspected of having Cush- ing’s syndrome (2, 51). | 59 | 7 | 7 | 7747e212ccc0adc57bc91241abdd93e50cf1b7c2ae748f8f3b089c99c82f199f |
Sensitivity for Cushing’s syndrome in pediatric patients is high ( 89%) (30). Thus, to achieve the goal of high sensitivity, we recommend using the upper limit of normal for the particular assay as the criterion for a positive test, provided the creatinine shows that the collection is complete and there is not excess... | 70 | 7 | 7 | 700751d55d8f7d3f88a81cde6057546ef449b2bd4a69be3e99ad6b8784eadeed |
For pediatric patients, the adult normal ranges may be used because most pediatric patients are of adult weight ( i.e. 45 kg). At the recommended cutoff point, false-positive elevations of UFC may be seen in several conditions. | 49 | 7 | 7 | d789ad0a7a393d01fddba55018b17ceaca56bef657df23383102ee77b9a0fde2 |
High fluid intake ( 5 liters/d) significantly increases UFC (52). Any physiological or pathological condition that increases cortisol production raises UFC (Table 2). Therefore, in these conditions a normal result is more reliable than an abnormal one. At the recommended cutoff point, false-negative results of urine ... | 67 | 7 | 7 | 5d6f8bab5f79ee976359a3d53947f3305fcf30c4c1fde7cc69b2941549c4a098 |
Because UFC reflects renal filtration, values are significantly lower in patients with moderate to severe renal impairment. A falsely low UFC can occur when creatinine clearance falls less than 60 ml/min, and UFC levels fall linearly with more severe renal failure (53). | 54 | 7 | 7 | da68c36f39488f744e6a8941643bdcc74410a2525ee43bead9d2a75b2e87c485 |
UFC can be normal if a patient has cyclic disease and collects urine when the disease is inactive. Finally, it may be normal in some patients with mild Cushing’s syndrome, in whom salivary cor- tisol may be more useful (54). | 54 | 7 | 7 | 8425a23e644ede87c2e279dc7c7e8797070035178db9b0cd346e1663c6363ca6 |
3.4.1 Remarks for UFC Sample collection and instructions It is important to ensure that patients provide a complete 24-h urine collection with appropriate total volume and urinary cre- atininelevels.Thismayrequirepatienteducationusingbothoral and written instructions. | 54 | 7 | 7 | ec3bf175b376c971e627e5043452d7056676d26d1efcc669070627d77ed82418 |
The first morning void is discarded so that the collection begins with an empty bladder. All subsequent voids throughout the day and night should be included in the collection, which is kept refrigerated (but not frozen), up to and including the first morning void on the second day. | 55 | 7 | 7 | 671ded7d362cccd2f776891eabdab41c7536c5354243425015c28eda878cf05c |
Once the bladderhasbeenemptiedintothecollectiononthesecondmorn- ing, the sample is complete. Patients should be instructed not to drink excessive amounts of fluid and to avoid the use of any glucocorticoid preparations, including steroid-containing skin or hemorrhoid creams, during TABLE 3. | 63 | 7 | 7 | 2698d4c9000b1bf8edef731365fd90470c0b77ef64af8352b7a4c05513cd549f |
Selected drugs that may interfere with the evaluation of tests for the diagnosis of Cushing’s syndrome a Drugs Drugs that accelerate dexamethasone metabolism by induction of CYP 3A4 Phenobarbital Phenytoin Carbamazepine Primidone Rifampin Rifapentine Ethosuximide Pioglitazone Drugs that impair dexamethasone metabolism ... | 212 | 7 | 7 | 6dab7a3a17e95475eb694766365a2b7f0c6f26114e4a30eff3f4f1915610a0fe |
Data regarding CYP3A4 obtained from http://medicine.iupui.edu/flockhart/table.htm. 1532 Nieman et al. Guidelines for the Diagnosis of Cushing’s Syndrome J Clin Endocrinol Metab, May 2008, 93(5):1526–1540 Downloaded from https://academic.oup.com/jcem/article/93/5/1526/2598096 by University of Wisconsin System user on 20... | 107 | 7 | 7 | 9f7974e4a0f883fce4bac0acd414951374bf407f368b22f7f9c2a46ef53e1f4c |
the collection. Because UFC levels in a patient with Cushing’s syndrome are variable, at least two collections should be per- formed, particularly in children in whom reproducibility can be low. | 41 | 8 | 8 | 52292ce31ef8f83ca01917ac2f403cc950d7f0233eda8a34b643993de825770c |
3.4.2 Evidence for late-night salivary cortisol In healthy individuals with stable conventional sleep-wake cy- cles, the level of serum cortisol begins to rise at 0300–0400 h, reaches a peak at 0700–0900 h, and then falls for the rest of the day to very low levels when the person is unstressed and asleep at midnight (5... | 81 | 8 | 8 | fa599e21d7905c20337feb7f22f961278b5254d3a01f8897830f2006d4c07ef9 |
The loss of circadian rhythm with absence of a late-night cortisol nadir is a consistent biochemical abnormality in patients with Cushing’s syndrome (56, 57). This difference in physiology forms the basis for measurement of a midnight serum or late-night salivary cortisol. | 58 | 8 | 8 | e4206156b5a81c1095f365852b1f777efe1bdaa898b1b3c0600c6ef2b81d5585 |
Biologically active free cortisol in the blood is in equilibrium with cortisol in the saliva, and the concentration of salivary cor- tisol does not appear to be affected by the rate of saliva produc- tion. | 44 | 8 | 8 | 7bcad8288a179ba51c08b1a655c575fb7f73b1bb9bd47f2e4e3d9b5f892d2405 |
Furthermore, an increase in blood cortisol is reflected by a change in the salivary cortisol concentration within a few min- utes (58). Various methods have been used to measure cortisol in the saliva, resulting in different reference ranges and yielding differences in sensitivity and specificity (59–67). | 58 | 8 | 8 | c68349eae98651cb823e30aee83d7566d17aabcde820320a9360ec22ee7f8389 |
The best-vali- datedassaysusedintheUnitedStatestomeasuresalivarycortisol are an ELISA and an assay performed by LC-MS/MS (28). | 40 | 8 | 8 | db1fd842253354fdae4069106f24458c6ec7e29931a36fbfca59a891b279fe82 |
When these two assay techniques are used, normal subjects usually have salivary cortisol levels at bedtime, or between 2300 and 2400 h, of less than 145 ng/dl (4 nmol/liter). | 43 | 8 | 8 | 89c89082655f0e2aabec96367fa0ae0f66315b050b60b9376d499ebaece68e22 |
Using a variety of assays and diagnostic criteria, investigators from different coun- tries have reported that late-night salivary cortisol levels yield a 92–100%sensitivityanda93–100%specificityforthediagnosis of Cushing’s syndrome (59–67). | 59 | 8 | 8 | a633dda3a457387037c937d4577cb8a61720a70b1801a11705e059c7742ab323 |
Overall, the evidence in adults suggeststhattheaccuracyofthistestissimilartothatofUFC(2). This easily performed, noninvasive test has been used in children to differentiate patients with Cushing’s syndrome from those with simple obesity. | 55 | 8 | 8 | 137616628d01a7a991707697833fd5fc751cdf59f5fc1a297d9feebf48c10a21 |
Investigators have reported high sensitivity (100%) and specificity (95.2%) for Cushing’s syndrome in this setting (68). The influence of gender, age, and coexisting medical condi- tions on the late-night salivary cortisol concentrations has not beenfullycharacterized.Itisimportanttonotethatthecircadian rhythm is blunt... | 102 | 8 | 8 | 154803a802b5aad2a103553985820bec20d7fb6321b0f4270a6d81f6fb343745 |
Other populations may have a high percentage of false-positive results. For example, in a study of men aged 60 yr or older, Liu et al. (72) reported that 20% of all participants and 40% of diabetichypertensivesubjectshadatleastoneelevatedlate-night salivary cortisol measurement. | 72 | 8 | 8 | 9bfaec46baa80a38b5f31b43aaa143ccc996e6bcebc72f72cb887604d4edca5a |
Using the upper reference range of each assay as the cutoff point, Baid et al. (28) measured bed- time salivary cortisol levels in a large number of obese subjects and found a specificity of only 85% when they used a RIA tech- nique, but a better specificity of 92% when tandem mass spec- trometry was used. | 74 | 8 | 8 | 1bc5ca56ff690422ad6a5b9ae6b7f00ec85e214ed6a9ad729605283677f974fc |
3.4.2 Remarks for late-night salivary cortisol Most clinicians using the late-night salivary cortisol test ask pa- tientstocollectasalivasampleontwoseparateeveningsbetween 2300 and 2400 h. | 53 | 8 | 8 | 9382ee79666f7e358d784977531b9110cee9450faf17fccc9563452e95a3d11a |
Saliva is collected either by passive drooling into a plastic tube or by placing a cotton pledget (salivette) in the mouth and chewing for 1–2 min. The sample is stable at room or refrigerator temperature for several weeks and can be mailed to a reference laboratory. | 58 | 8 | 8 | 9e3323f6c87832cef5611903d0ea955151885084e1b8ece88eec2259ee10d1f7 |
Reports show good correlation between salivary and simultaneous serum cortisol values in healthy vol- unteers(73,74).Whensampleswereobtainedatthesamesitting, those collected using the salivette device had lower cortisol con- centrations than those collected from passive drooling, but they correlated better with total a... | 73 | 8 | 8 | 1df8a1c77e9f4ff6b975a2372006de76614661d671078ffd814ce1b8fc71631f |
Several factors that affect the salivary cortisol test should be considered when evaluating the results. The salivary glands ex- press 11 -hydroxysteroid dehydrogenase type 2 (11 -HSD2), which converts the biologically active cortisol to inactive corti- sone (75). | 64 | 8 | 8 | 72d9b6820f7a1aae15e5fcd1753b4e90acaab829dead213f62fe036f96f7c61e |
It is theoretically possible that individuals using lico- rice or chewing tobacco (both of which contain the 11 -hydrox- ysteroid dehydrogenase type 2 inhibitor glycyrrhizic acid) may have a falsely elevated late-night salivary cortisol. | 57 | 8 | 8 | aa13f0504c18767b09fc013d92c2391b4b9a338276fcae439efcc3f5e0f2c130 |
Patients who smoke cigarettes also have been shown to have higher late-night salivary cortisol measurements than do nonsmokers (76). Al- though the duration of this effect is not known, it seems prudent to avoid cigarette smoking on the day of collection. | 53 | 8 | 8 | 58af8e6cb6fcedb8e10af038240ebb5b7b322b93e31d77a10097641f612e9e0a |
Direct con- tamination of the salivette by steroid-containing lotion or oral gels also may result in false-positive results. Because the test assumes a nadir of cortisol in the late evening, it may not be appropriate for shift workers or those with variable bedtimes, and the timing of the collection should be adjusted ... | 87 | 8 | 8 | c0d70350c58e9c158816cdec631e25c38d57beea40c9d248579077b9e57693d2 |
Similarly, nocturnal salivary cortisols may be transiently abnor- mal in individuals crossing widely different time zones. Finally, stress immediately before the collection also may increase sali- vary cortisol physiologically; therefore, ideally, samples should be collected on a quiet evening at home (64). | 62 | 8 | 8 | 984695e12961f03d4256ed4b9c0f4148481382af50a70986a1a3b8819a9c9f9c |
Theoretically, contamination with blood might increase sal- ivary cortisol levels. Although Kivlighan et al. (77) reported that minor to moderate blood leakage as a result of vigorous tooth brushing had no effect on salivary cortisol values, the possible effect of gingivitis or oral sores or injury is not known. | 70 | 8 | 8 | 16de53d9cf3aa0bc4e9029a7b6bf467da0bba13ee31f5006fb407df2aa028bae |
3.4.3 Evidence for the 1-mg DST In normal subjects, the administration of a supraphysiological dose of glucocorticoid results in suppression of ACTH and cor- tisol secretion. | 45 | 8 | 8 | bb2446a44c618172787d0d414eba9b07a40adf90082f511564b36da24d767f75 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.