The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism
Open accessAbstract
Background: Diagnosing endogenous hypercortisolism remains a challenge, partly due to a lack of biochemical tests with good diagnostic accuracy. Objectives: To evaluate the diagnostic value of salivary cortisol and cortisone in patients with suspected hypercortisolism. Methods: Retrospective study including 155 patients with adrenal incidentaloma, and 54 patients with suspected Cushing´s syndrome (CS). Salivary samples were collected at home, at 11 p.m., and at 8 a.m. following an over-night dexamethasone suppression test (DST). Salivary cortisol and cortisone were measured with liquid chromatography-tandem mass spectrometry. Results: Ten of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS). Using previously established cut-offs, all patients with ACS had elevated plasma-cortisol (>50 nmol/L) following DST, 9/10 had elevated late-night salivary cortisone (>15 nmol/L) whereas only 4/10 had elevated late-night salivary cortisol (LNSC; >3 nmol/L) compared to 35%, 9% and 8%, respectively, of the 145 patients with non-functioning adrenal incidentaloma. Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8 a.m. following DST compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma. One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST. Conclusion: LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism. Instead, late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma and salivary cortisone at 8 a.m. following DST in patients with suspected CS. Larger studies are needed to confirm these findings.
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Written from the paper’s full text.
TL;DR
In a retrospective study of patients with adrenal incidentaloma or suspected Cushing’s syndrome, late-night salivary cortisol (LNSC) had low sensitivity for autonomous cortisol secretion (ACS), while late-night salivary cortisone and post-dexamethasone salivary cortisol/cortisone showed better diagnostic performance. The authors conclude LNSC alone is not sufficient for screening suspected hypercortisolism, but salivary cortisone is promising and needs larger confirmatory studies.
Key findings
- Among 155 patients with adrenal incidentaloma, 10 had ACS. Late-night salivary cortisone >15 nmol/L identified 9/10 ACS patients (90% sensitivity, 91% specificity), whereas LNSC >3 nmol/L identified only 4/10 (40% sensitivity, 92% specificity); post-DST plasma cortisol >50 nmol/L identified 10/10 but had 65% specificity.
- In 54 patients with suspected Cushing’s syndrome, CS was confirmed in 7. Post-DST salivary cortisone >5 nmol/L had 100% sensitivity and 91% specificity, post-DST salivary cortisol >1 nmol/L had 100% sensitivity and 84% specificity, and LNSC >3 nmol/L had 83% sensitivity and 91% specificity.
- One patient with CS had normal LNSC and one had normal late-night salivary cortisone, but all seven patients with CS had elevated salivary cortisol and cortisone at 8 a.m. following DST.
- The authors conclude LNSC is not sufficiently sensitive or specific for screening suspected hypercortisolism, while late-night salivary cortisone in adrenal incidentaloma and post-DST salivary cortisone in suspected CS appear promising.
Methods
- Retrospective single-center study at Sahlgrenska University Hospital including patients who provided salivary samples between April 2018 and November 2020; final analysis included 155 patients with adrenal incidentaloma and 54 with suspected Cushing’s syndrome.
- Patients collected home saliva samples at 11 p.m. and at 8 a.m. after a 1-mg overnight dexamethasone suppression test (DST); salivary cortisol and cortisone were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), with contamination assessed by salivary cortisol:cortisone ratio.
- ACS diagnosis was based on real-life clinical assessment without predefined criteria; CS diagnosis required clinical symptoms plus at least two biochemical screening tests showing hypercortisolism. ROC/AUC analyses were performed, with DeLong tests comparing salivary tests against post-DST plasma cortisol.
Limitations
- The paper states limitations including the limited number of patients, especially those finally diagnosed with CS; inconsistent collection of two or more saliva samples in all suspected CS patients; retrospective design with no predefined ACS criteria and diagnosis by several physicians, risking diagnostic inconsistency; clinicians were not blinded to salivary results; and plasma dexamethasone was not measured.
- Evident from the text: the single-center retrospective design and reliance on clinical diagnosis may limit generalizability, and the very small ACS and CS groups make sensitivity and specificity estimates imprecise.
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Claims the paper makes
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- Findingown data
One patient with CS had P-cortisol <138 nmol/L following DST.
“One patient with CS had P-cortisol <138 nmol/L following DST, one had normal LNSC and one had normal late-night salivary cortisone”
Quote in the paperNot a substantial claim - Findingown data
Among patients with non-functioning adrenal incidentaloma, 8% had elevated salivary cortisone at 8 a.m. following DST.
“compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma.”
Quote in the paperNot a substantial claim - Findingown data
9 of 10 patients with ACS had elevated late-night salivary cortisone (>15 nmol/L).
“9/10 had elevated late-night salivary cortisone (>15 nmol/L)”
Quote in the paperSubstantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol >138 nmol/L after DST (n=15), 40% had salivary cortisol at 8 a.m. following DST >1 nmol/L.
“6 (40%) had salivary cortisol at 8 a.m. following DST >1 nmol/L”
Quote in the paperSubstantial claim - Findingown data
6 of 10 patients with ACS had elevated salivary cortisol at 8 a.m. following DST.
“Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8 a.m. following DST”
Quote in the paperSubstantial claim
- Findingown data
4 of 10 patients with ACS had elevated late-night salivary cortisol (LNSC; >3 nmol/L).
“only 4/10 had elevated late-night salivary cortisol (LNSC; >3 nmol/L)”
Quote in the paperSubstantial claim - Findingown data
In ROC analysis for patients with adrenal incidentaloma, the greatest AUC was found for P-cortisol following DST and late-night Sa-cortisone.
“In a ROC analysis, the greatest AUC was found for P-cortisol following DST and late-night Sa-cortisone ( Figure 2 ).”
Quote in the paperSubstantial claim - Findingown data
CS was ruled out in 47 (87%) patients with suspected CS.
“CS was ruled out in 47 (87%) patients and confirmed in 7 (13%) patients”
Quote in the paperNot a substantial claim - Findingown data
Among patients with non-functioning adrenal incidentaloma, 9% had elevated salivary cortisol at 8 a.m. following DST.
“compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma.”
Quote in the paperNot a substantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol >138 nmol/L after DST (n=15), 13% had LNSC >3 nmol/L.
“of patients with P-cortisol >138 nmol/L after DST (n=15), two (13%) had LNSC >3 nmol/L”
Quote in the paperNot a substantial claim - Findingown data
CS was confirmed in 7 (13%) patients with suspected CS.
“CS was ruled out in 47 (87%) patients and confirmed in 7 (13%) patients”
Quote in the paperNot a substantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol <138 nmol/L after DST (n=140), 8% had LNSC >3 nmol/L.
“Among the patients with P-cortisol < 138 nmol/L after DST (n=140), LNSC was >3 nmol/L in 11 (8%)”
Quote in the paperNot a substantial claim - Findingown data
All 6 patients with overt CS had increased salivary cortisol following DST.
“One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST.”
Quote in the paperSubstantial claim - Findingown data
All 6 patients with overt CS had increased salivary cortisone following DST.
“One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST.”
Quote in the paperSubstantial claim - Findingown data
Among the 145 patients with non-functioning adrenal incidentaloma, 35% had post-DST plasma cortisol >50 nmol/L.
“Of 145 patients with non-functioning adrenal adenoma, 51 (35%) had P-cortisol >50 nmol/L”
Quote in the paperNot a substantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol >138 nmol/L after DST (n=15), 47% had late-night Sa-cortisone >15 nmol/L.
“7 (47%) had late-night Sa-cortisone >15 nmol/L”
Quote in the paperSubstantial claim - Findingown data
All 10 patients with ACS had elevated plasma cortisol (>50 nmol/L) following DST.
“Using previously established cut-offs, all patients with ACS had elevated plasma-cortisol (>50 nmol/L) following DST”
Quote in the paperSubstantial claim - Findingown data
One of 6 patients with overt CS had normal late-night salivary cortisone.
“One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST.”
Quote in the paperSubstantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol >138 nmol/L after DST (n=15), 67% had salivary cortisone at 8 a.m. following DST >3 nmol/L.
“10 (67%) had salivary cortisone at 8 a.m. following DST >3 nmol/L”
Quote in the paperSubstantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol <138 nmol/L after DST (n=140), 6% had salivary cortisol at 8 a.m. following DST >1 nmol/L.
“salivary cortisol at 8 a.m. following DST >1 nmol/L in 9 (6%)”
Quote in the paperSubstantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol <138 nmol/L after DST (n=140), 10% had late-night Sa-cortisone >15 nmol/L.
“late-night Sa-cortisone >15 nmol/L in 14 (10%)”
Quote in the paperSubstantial claim - Findingown data
One of 6 patients with overt CS had a normal LNSC.
“One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST.”
Quote in the paperSubstantial claim - Findingown data
Among the 145 patients with non-functioning adrenal incidentaloma, 9% had late-night salivary cortisone >15 nmol/L.
“13 (9%) had late-night Sa-cortisone >15 nmol/L”
Quote in the paperSubstantial claim - Findingown data
One patient with CS had normal LNSC.
“One patient with CS had P-cortisol <138 nmol/L following DST, one had normal LNSC and one had normal late-night salivary cortisone”
Quote in the paperSubstantial claim - Findingown data
Among the 155 patients with adrenal incidentaloma, 145 (94%) were considered to have non-functioning adrenal adenoma.
“Among the 155 patients with adrenal incidentaloma, 145 (94%) were considered to have non-functioning adrenal adenoma and 10 (6%) to have ACS.”
Quote in the paperNot a substantial claim - Findingown data
6 of 10 patients with ACS had elevated salivary cortisone at 8 a.m. following DST.
“Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8 a.m. following DST”
Quote in the paperSubstantial claim - Findingown data
In this study, 10 of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS).
“Ten of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS).”
- Also stated in: § Patients with adrenal incidentalomas · plain
“Among the 155 patients with adrenal incidentaloma, 145 (94%) were considered to have non-functioning adrenal adenoma and 10 (6%) to have ACS.”
Quote in the paperNot a substantial claim - Also stated in: § Patients with adrenal incidentalomas · plain
- Findingown data
No significant differences were found between the AUCs for the salivary tests and the AUC for P-cortisol following DST in patients with adrenal incidentaloma.
“However, no significant differences were found between the AUCs for the salivary tests and the AUC for P-cortisol following DST.”
Quote in the paperSubstantial claim - Findingown data
Among patients with adrenal incidentaloma and P-cortisol <138 nmol/L after DST (n=140), 23% had salivary cortisone at 8 a.m. following DST >3 nmol/L.
“salivary cortisone at 8 a.m. following DST >3 nmol/L in 32 (23%)”
Quote in the paperSubstantial claim - Findingown data
P-cortisol following DST at 107 nmol/L gave the best combination of high sensitivity (90%) and specificity (92%) in patients with adrenal incidentaloma.
“P-cortisol following DST at 107 nmol/L gave the best combination of high sensitivity (90%) and specificity (92%).”
Quote in the paperSubstantial claim - Findingown data
For diagnosing CS in patients with suspected CS, post-DST Sa-cortisol >1 nmol/L had sensitivity 100% and specificity 84%.
“| Post-DST Sa-cortisol >1 nmol/L | 7/43 (16%) | 7/7 (100%) | <0.001 | 100% | 84% |”
Quote in the paperSubstantial claim - Findingown data
For diagnosing CS in patients with suspected CS, post-DST Sa-cortisone >5 nmol/L had sensitivity 100% and specificity 91%.
“| Post-DST Sa-cortisone >5 nmol/L | 4/43 (9%) | 7/7 (100%) | <0.001 | 100% | 91% |”
Quote in the paperSubstantial claim - Findingown data
For diagnosing ACS in patients with adrenal incidentaloma, post-DST Sa-cortisone >5 nmol/L had sensitivity 60% and specificity 92%.
“| Post-DST Sa-cortisone >5 nmol/L | 11 (8)*** | 6 (60) | <0.001 | 60% | 92% |”
Quote in the paperSubstantial claim - Findingown data
For diagnosing ACS in patients with adrenal incidentaloma, post-DST Sa-cortisol >1 nmol/L had sensitivity 60% and specificity 91%.
“| Post-DST Sa-cortisol >1 nmol/L | 12 (9)*** | 6 (60) | <0.001 | 60% | 91% |”
Quote in the paperSubstantial claim - Findingown data
For diagnosing ACS in patients with adrenal incidentaloma, LNSC >3 nmol/L had sensitivity 40% and specificity 92%.
“| LNSC >3 nmol/L | 11 (8)** | 4 (40) | 0.009 | 40% | 92% |”
Quote in the paperSubstantial claim - Findingown data
LNSC has a low sensitivity for diagnosing ACS in patients with adrenal incidentaloma.
“Our findings suggest that LNSC has a low sensitivity for diagnosing ACS in patients with adrenal incidentaloma whereas Sa-cortisone at 11 p.m. had a high sensitivity and specificity for diagnosing the disorder.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
Following DST, all seven patients with CS had Sa-cortisone above the normal range.
“Following DST, all seven patients with CS had Sa-cortisol and cortisone above the normal range.”
Quote in the paperSubstantial claim - Findingown data
Following DST, all seven patients with CS had Sa-cortisol above the normal range.
“Following DST, all seven patients with CS had Sa-cortisol and cortisone above the normal range.”
Quote in the paperSubstantial claim - Findingown data
For diagnosing CS in patients with suspected CS, LNSC >3 nmol/L had sensitivity 83% and specificity 91%.
“| LNSC >3 nmol/L | 4/45 (9%) | 5/6 (83%) | <0.001 | 83% | 91% |”
Quote in the paperSubstantial claim - Findingown data
For diagnosing ACS in patients with adrenal incidentaloma, late-night Sa-cortisone >15 nmol/L had sensitivity 90% and specificity 91%.
“| Late-night Sa-cortisone >15 nmol/L | 13 (9)** | 9 (90) | <0.001 | 90% | 91% |”
Quote in the paperSubstantial claim - Findingown data
For diagnosing CS in patients with suspected CS, late-night Sa-cortisone >15 nmol/L had sensitivity 83% and specificity 93%.
“| Late-night Sa-cortisone >15 nmol/L | 3/45 (7%) | 5/6 (83%) | <0.001 | 83% | 93% |”
Quote in the paperSubstantial claim - Findingown data
One patient with CS had normal late-night salivary cortisone.
“One patient with CS had P-cortisol <138 nmol/L following DST, one had normal LNSC and one had normal late-night salivary cortisone”
Quote in the paperNot a substantial claim - Findingown data
Sa-cortisone at 11 p.m. had a high sensitivity and specificity for diagnosing ACS in patients with adrenal incidentaloma.
“Our findings suggest that LNSC has a low sensitivity for diagnosing ACS in patients with adrenal incidentaloma whereas Sa-cortisone at 11 p.m. had a high sensitivity and specificity for diagnosing the disorder.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
UFC was normal in three out of six patients with CS.
“Moreover, UFC was normal in three out of six patients”
Quote in the paperSubstantial claim - Findingown data
In the current study, one patient with overt CS had P-cortisol <138 nmol/L following DST.
“In the current study, one patient with overt CS had normal LNSC, another had P-cortisol <138 nmol/L following DST and half of the patients had normal UFC.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
All patients in our study diagnosed with ACS had P-cortisol >50 nmol/L on the DST.
“Indeed, all patients in our study diagnosed with ACS had P-cortisol >50 nmol/L on the DST, supporting a high negative predictive value of P-cortisol <50 nmol/L.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
40% of the patients diagnosed with ACS in our cohort had P-cortisol <138 nmol/L following DST.
“However, 40% of the patients diagnosed with ACS in our cohort had P-cortisol <138 nmol/L following DST, illustrating a relatively poor ability to confirm the diagnosis by using this cut-off.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
In our study, 10% of all patients with adrenal incidentalomas had P-cortisol >138 nmol/L.
“In our study, 10% of all patients with adrenal incidentalomas had P-cortisol >138 nmol/L, providing a more reasonable prevalence of ACS in comparison to a cut-off of 50 nmol/L.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
In the current study, one patient with overt CS had normal LNSC.
“In the current study, one patient with overt CS had normal LNSC, another had P-cortisol <138 nmol/L following DST and half of the patients had normal UFC.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingcitation
LNSC and Sa-cortisone at 11 p.m. had a slightly lower sensitivity than salivary samples collected after DST.
“Also, in agreement with Bäcklund et al. (17), LNSC and Sa-cortisone at 11 p.m. had a slightly lower sensitivity than salivary samples collected after DST.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
In our study, 35% of patients with non-functioning adrenal incidentaloma had P-cortisol >50 nmol/L following DST.
“In our study, 35% of patients with non-functioning adrenal incidentaloma had P-cortisol >50 nmol/L following DST, i.e., a “false positive test”, in agreement with previous rapports (6).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Sherlock, 2020, Adrenal incidentaloma, Endocr Rev source
Not checked in the free run.
- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
All patients with overt CS had elevated Sa-cortisol as well as Sa-cortisone at 8 a.m. following DST.
“Interestingly, however, all patients with overt CS had elevated Sa-cortisol as well as Sa-cortisone at 8 a.m. following DST.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
Sa-cortisol and Sa-cortisone were inadequately suppressed following DST in 6 of 10 patients with ACS.
“Sa-cortisol and Sa-cortisone were inadequately suppressed following DST in 6 of 10 patients with ACS, whereas inadequate suppression of Sa-cortisol and Sa-cortisone was found only in 9 and 8%, respectively, of patients with non-functioning adrenal incidentalomas, giving a specificity of 91/92%.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
In the current study, half of the patients with overt CS had normal UFC.
“In the current study, one patient with overt CS had normal LNSC, another had P-cortisol <138 nmol/L following DST and half of the patients had normal UFC.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Findingown data
In our study, 9 of 10 patients with ACS had elevated Sa-cortisone at 11 p.m.
“Our study, showing that 9 of 10 patients with ACS had elevated Sa-cortisone at 11 p.m., suggest that Sa-cortisone may be of greater diagnostic value than LNSC also in patients with adrenal incidentaloma.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Interpretationown data
Salivary cortisone at 8 a.m. following DST seems promising in patients with suspected CS.
“salivary cortisone at 8 a.m. following DST in patients with suspected CS.”
Quote in the paperSubstantial claim - Interpretationown data
LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism.
“LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism.”
Quote in the paperSubstantial claim - Interpretationown data
Late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma.
“Instead, late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma”
Quote in the paperSubstantial claim - Interpretationown data
In patients with suspected CS, the best diagnostic performance in terms of high sensitivity (100%) in combination with high specificity (91%) for diagnosing CS was achieved by using Sa-cortisone following DST.
“The best diagnostic performance in terms of high sensitivity (100%) in combination with high specificity (91%) for diagnosing CS was achieved by using Sa-cortisone following DST ( Table 3 ).”
Quote in the paperSubstantial claim - Interpretationown data
In patients with adrenal incidentaloma, the best diagnostic performance in terms of high sensitivity (90%) in combination with high specificity (91%) for diagnosing ACS was achieved by using late-night Sa-cortisone.
“Thus, in patients with adrenal incidentaloma the best diagnostic performance in terms of high sensitivity (90%) in combination with high specificity (91%) for diagnosing ACS was achieved by using late-night Sa-cortisone ( Table 1 ).”
Quote in the paperSubstantial claim - Premisecitation
The upper limit of normal for LNSC used in this study was <3 nmol/L.
“- LNSC <3 nmol/L”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- Premisecitation
All previous studies, regardless of analytical assay, have concluded that LNSC cannot be recommended as an exclusive screening method for ACS.
“In fact, due to the low sensitivity, all previous studies, regardless of analytical assay, have concluded that LNSC cannot be recommended as an exclusive screening method for ACS (11–16).”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [11] Masserini, 2009, The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma, Eur J Endocrinol source
Not checked in the free run.
- cites [12] Palmieri, 2013, The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism, Eur J Endocrinol source
Not checked in the free run.
- cites [13] Ceccato, 2017, First-line screening tests for cushing's syndrome in patients with adrenal incidentaloma: The role of urinary free cortisol measured by LC-MS/MS, J Endocrinol Invest source
Not checked in the free run.
- cites [14] Araujo-Castro, 2021, Diagnostic accuracy of the different hormonal tests used for the diagnosis of autonomous cortisol secretion, Sci Rep source
Not checked in the free run.
- cites [15] Ueland, 2020, Diagnostic testing of autonomous cortisol secretion in adrenal incidentalomas, Endocr Connect source
Not checked in the free run.
- cites [16] Ceccato, 2018, Daily salivary cortisol and cortisone rhythm in patients with adrenal incidentaloma, Endocrine source
Not checked in the free run.
- Premisecitation
In one study, Sa-cortisol <2.8 nmol/L at 11 p.m. had 31% sensitivity and 83% specificity for diagnosing ACS in 70 patients with adrenal incidentaloma.
“In one of these studies, the sensitivity of Sa-cortisol <2.8 nmol/L at 11 p.m. was 31%, and the specificity was 83%, for diagnosing ACS in 70 patients with adrenal incidentaloma (12), i.e. in line with the current study.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Palmieri, 2013, The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism, Eur J Endocrinol source
Not checked in the free run.
- Premisecitation
The upper limit of normal for Sa-cortisol at 8 a.m. following DST used in this study was <1 nmol/L.
“- Sa-cortisol at 8 a.m. following DST <1 nmol/L”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- Premisecitation
Diagnosing CS and ACS in patients with adrenal incidentaloma remains a challenge, partly due to a lack of biochemical tests with high diagnostic accuracy.
“Diagnosing Cushing’s syndrome (CS) and autonomous cortisol secretion (ACS) in patients with adrenal incidentaloma remains a challenge, partly due to a lack of biochemical tests with high diagnostic accuracy (1, 2).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [1] Fassnacht, 2016, Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors, Eur J Endocrinol source
Not checked in the free run.
- cites [2] Nieman, 2008, The diagnosis of cushing's syndrome: An endocrine society clinical practice guideline, J Clin Endocrinol Metab source
Not checked in the free run.
- Premisecitation
Currently, there is no consensus regarding diagnostic criteria for ACS.
“Currently, there is no consensus regarding diagnostic criteria for ACS (6).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Sherlock, 2020, Adrenal incidentaloma, Endocr Rev source
Not checked in the free run.
- Premisecitation
The low specificity of DST for diagnosing CS and ACS is problematic.
“However, the low specificity of DST for diagnosing CS and ACS is problematic (6).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Sherlock, 2020, Adrenal incidentaloma, Endocr Rev source
Not checked in the free run.
- Premisecitation
The upper limit of normal for Sa-cortisone at 11 p.m. used in this study was <15 nmol/L.
“- Sa-cortisone at 11 p.m. <15 nmol/L”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- Premisecitation
In general, p-cortisol following DST >138 nmol/L was considered highly suggestive for hypercortisolism.
“In general, p-cortisol following DST <50 nmol/L was considered to exclude hypercortisolism, while values >138 nmol/L were considered to be highly suggestive for hypercortisolism (1, 2).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [1] Fassnacht, 2016, Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors, Eur J Endocrinol source
Not checked in the free run.
- cites [2] Nieman, 2008, The diagnosis of cushing's syndrome: An endocrine society clinical practice guideline, J Clin Endocrinol Metab source
Not checked in the free run.
- Premisecitation
In most studies, LNSC was analyzed with immunochemical methods, which have lower analytical specificity than LC-MS/MS due to a risk of cross-reactions between cortisol and other steroid metabolites.
“In most of these studies LNSC was analyzed with immunochemical methods, i.e. methods with lower analytical specificity than LC-MS/MS due to a risk of cross-reactions between cortisol and other steroid metabolites (19, 20).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [19] Mészáros, 2018, Diagnostic performance of a newly developed salivary cortisol and cortisone measurement using an LC-MS/MS method with simple and rapid sample preparation, J Endocrinol Invest source
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- cites [20] Israelsson, 2018, 20α- and 20β-dihydrocortisone may interfere in LC-MS/MS determination of cortisol in saliva and urine, Ann Clin Biochem source
Not checked in the free run.
- Premisecitation
The upper limit of normal for Sa-cortisone at 8 a.m. following DST used in this study was <5 nmol/L.
“- Sa-cortisone at 8 a.m. following DST <5 nmol/L”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- Premisecitation
The diagnostic value of LNSC for detecting ACS in patients with adrenal incidentaloma is less well established.
“The diagnostic value of LNSC for detecting ACS in patients with adrenal incidentaloma is, however, less well established (6).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Sherlock, 2020, Adrenal incidentaloma, Endocr Rev source
Not checked in the free run.
- Premisecitation
LNSC is well-established as a first-line screening test for patients with CS.
“LNSC is well-established as a first-line screening test for patients with CS (7–10).”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [7] Raff, 1998, Late-night salivary cortisol as a screening test for cushing's syndrome, J Clin Endocrinol Metab source
Not checked in the free run.
- cites [8] Mohamed, 2022, Late-night salivary cortisol and cortisone should be the initial screening test for cushing's syndrome, Endocr Connect source
Not checked in the free run.
- cites [9] Kannankeril, 2020, Prospective evaluation of late-night salivary cortisol and cortisone by EIA and LC-MS/MS in suspected cushing syndrome, J Endocr Soc source
Not checked in the free run.
- cites [10] Ponzetto, 2020, Reference ranges of late-night salivary cortisol and cortisone measured by LC-MS/MS and accuracy for the diagnosis of cushing's syndrome, J Endocrinol Invest source
Not checked in the free run.
- Interpretationown data
In patients with suspected CS, Sa-cortisone following DST seems to be a promising diagnostic alternative.
“Furthermore, in patients with suspected CS, Sa-cortisone following DST seem to be a promising diagnostic alternative.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Interpretationown data
P-cortisol <50 nmol/L has a high negative predictive value for ACS.
“Indeed, all patients in our study diagnosed with ACS had P-cortisol >50 nmol/L on the DST, supporting a high negative predictive value of P-cortisol <50 nmol/L.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Study design and conductreasoning
It is difficult to evaluate independently the diagnostic value of each biochemical test, including salivary cortisol and cortisone, because clinicians were not blinded.
“Moreover, since the treating clinicians were not blinded to the results of the salivary samples when diagnosing ACS and CS, it is difficult to evaluate independently the diagnostic value of each biochemical test, including salivary cortisol and cortisone.”
Quote in the paperSubstantial claim - Interpretationown data
DST should not be the only biochemical test used to diagnose mild autonomous hypercortisolism, regardless of the cut-off value used.
“Our results, therefore, indicate that DST should not be the only biochemical test used to diagnose mild autonomous hypercortisolism, regardless of the cut-off value used.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Study design and conductreasoning
Due to lack of predefined specific criteria, the risk of diagnostic inconsistency cannot be ruled out.
“Due to the lack of predefined specific criteria, the risk of diagnostic inconsistency cannot be ruled out.”
Quote in the paperSubstantial claim - Study design and conductnone given
Treating clinicians were not blinded to the results of the salivary samples when diagnosing ACS and CS.
“Moreover, since the treating clinicians were not blinded to the results of the salivary samples when diagnosing ACS and CS, it is difficult to evaluate independently the diagnostic value of each biochemical test, including salivary cortisol and cortisone.”
Quote in the paperSubstantial claim - Interpretationown data
The DST has low specificity.
“The downside of this test is, however, the low specificity.”
Quote in the paperSubstantial claim - Study design and conductnone given
Two or more saliva samples were not consequently sampled in all patients with suspected CS.
“The limitations of this study include the limited number of patients, especially the group of patients finally diagnosed with CS, and that two or more saliva samples were not consequently sampled in all patients with suspected CS, emphasizing the need for caution when interpreting the results.”
Quote in the paperNot a substantial claim - Study design and conductown data
The study had a limited number of patients, especially in the group finally diagnosed with CS.
“The limitations of this study include the limited number of patients, especially the group of patients finally diagnosed with CS, and that two or more saliva samples were not consequently sampled in all patients with suspected CS, emphasizing the need for caution when interpreting the results.”
Quote in the paperSubstantial claim - Premisecitation
Bäcklund et al. found that Sa-cortisone at 11 p.m. had a higher sensitivity than LNSC for diagnosing CS.
“Bäcklund et al. recently found that Sa-cortisone at 11 p.m. had a higher sensitivity than LNSC for diagnosing CS (17).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- Interpretationown data
Using a cut-off of P-cortisol >138 nmol/L provides a more reasonable prevalence of ACS in comparison to a cut-off of 50 nmol/L.
“In our study, 10% of all patients with adrenal incidentalomas had P-cortisol >138 nmol/L, providing a more reasonable prevalence of ACS in comparison to a cut-off of 50 nmol/L.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Interpretationown data
Using a cut-off of P-cortisol >138 nmol/L has a relatively poor ability to confirm the diagnosis of ACS.
“However, 40% of the patients diagnosed with ACS in our cohort had P-cortisol <138 nmol/L following DST, illustrating a relatively poor ability to confirm the diagnosis by using this cut-off.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- Interpretationown data
Sa-cortisone may be of greater diagnostic value than LNSC in patients with adrenal incidentaloma.
“Our study, showing that 9 of 10 patients with ACS had elevated Sa-cortisone at 11 p.m., suggest that Sa-cortisone may be of greater diagnostic value than LNSC also in patients with adrenal incidentaloma.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 22
- May combine two claims. 17
The quote only partly states this claim.
Findingown dataAmong the 145 patients with non-functioning adrenal incidentaloma, 8% had LNSC >3 nmol/L.
“Eleven of 143 (8%) patients with non-functioning adrenal adenoma had LNSC >3 nmol/L”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Findingown dataIn total, 54 patients with suspected CS were included in the analysis.
“In total, 54 patients, 45 women (87%) and 9 men (13%), with suspected CS were included in the analysis.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOf the 7 confirmed CS patients, 4 had Cushing's disease, two had cortisol-producing adrenal adenoma, and one had ectopic CS.
“CS was ruled out in 47 (87%) patients and confirmed in 7 (13%) patients, 4 with Cushing’s disease, two with cortisol-producing adrenal adenoma and one with ectopic CS”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe specificity of Sa-cortisol and Sa-cortisone following DST for ACS was 91% and 92%, respectively.
“Sa-cortisol and Sa-cortisone were inadequately suppressed following DST in 6 of 10 patients with ACS, whereas inadequate suppression of Sa-cortisol and Sa-cortisone was found only in 9 and 8%, respectively, of patients with non-functioning adrenal incidentalomas, giving a specificity of 91/92%.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
May combine two claims.
Findingown dataIn patients with non-functioning adrenal incidentalomas, inadequate suppression of Sa-cortisol and Sa-cortisone following DST was found in 9% and 8%, respectively.
“Sa-cortisol and Sa-cortisone were inadequately suppressed following DST in 6 of 10 patients with ACS, whereas inadequate suppression of Sa-cortisol and Sa-cortisone was found only in 9 and 8%, respectively, of patients with non-functioning adrenal incidentalomas, giving a specificity of 91/92%.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
May combine two claims.
PremisecitationSalivary cortisone at 11 p.m., as well as salivary cortisol and cortisone at 8 a.m. following 1-mg overnight DST, all have high diagnostic accuracy for CS.
“We have recently demonstrated that salivary cortisone at 11 p.m., as well as salivary cortisol and cortisone at 8 a.m. following 1-mg overnight DST, all have high diagnostic accuracy for CS (17).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUpon clinical suspicion of CS, current guidelines recommend biochemical screening with either a 1 mg overnight DST, 24-hour urinary free-cortisol or LNSC.
“Upon clinical suspicion of CS, current guidelines recommend biochemical screening with either a 1 mg overnight dexamethasone suppression test (DST), 24-hour urinary free-cortisol or late-night salivary cortisol (LNSC) (2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Nieman, 2008, The diagnosis of cushing's syndrome: An endocrine society clinical practice guideline, J Clin Endocrinol Metab source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLC-MS/MS has only been used three times before for measuring LNSC in patients with adrenal incidentaloma.
“To our knowledge, LC-MS/MS has only been used three times before for measuring LNSC in patients with adrenal incidentaloma (12, 15, 16).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [12] Palmieri, 2013, The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism, Eur J Endocrinol source
Not checked in the free run.
- cites [15] Ueland, 2020, Diagnostic testing of autonomous cortisol secretion in adrenal incidentalomas, Endocr Connect source
Not checked in the free run.
- cites [16] Ceccato, 2018, Daily salivary cortisol and cortisone rhythm in patients with adrenal incidentaloma, Endocrine source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationThe limited number of studies published to date have shown that LNSC has a relatively low sensitivity for predicting ACS, and subsequently conclude that the test is not suitable for screening of this disorder.
“The limited number of studies published to date have shown that LNSC has a relatively low sensitivity for predicting ACS, and subsequently conclude that the test is not suitable for screening of this disorder (11–16).”
Quote in the paperSubstantial claim0 of 6 sources checked- cites [11] Masserini, 2009, The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma, Eur J Endocrinol source
Not checked in the free run.
- cites [12] Palmieri, 2013, The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism, Eur J Endocrinol source
Not checked in the free run.
- cites [13] Ceccato, 2017, First-line screening tests for cushing's syndrome in patients with adrenal incidentaloma: The role of urinary free cortisol measured by LC-MS/MS, J Endocrinol Invest source
Not checked in the free run.
- cites [14] Araujo-Castro, 2021, Diagnostic accuracy of the different hormonal tests used for the diagnosis of autonomous cortisol secretion, Sci Rep source
Not checked in the free run.
- cites [15] Ueland, 2020, Diagnostic testing of autonomous cortisol secretion in adrenal incidentalomas, Endocr Connect source
Not checked in the free run.
- cites [16] Ceccato, 2018, Daily salivary cortisol and cortisone rhythm in patients with adrenal incidentaloma, Endocrine source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductreasoningNo predefined diagnostic criteria for ACS were used; instead, the diagnosis was provided through a real-life clinical assessment made by the treating endocrinologist.
“Therefore, in this study, no predefined diagnostic criteria were used. Instead, the diagnosis was provided through a real-life clinical assessment made by the treating endocrinologist.”
Quote in the paperSubstantial claim- Rests on an assumption: The real-life clinical assessment made by the treating endocrinologist correctly classifies patients with adrenal incidentaloma as having ACS or non-functioning adrenal incidentaloma.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn a recent study from Norway, salivary cortisone at 8 a.m. following 1-mg overnight DST was found to be useful in patients with hypercortisolism, both CS and ACS.
“Also, in a recent study from Norway, salivary cortisone at 8 a.m. following 1-mg overnight DST was found to be useful in patients with hypercortisolism, both CS and ACS (18).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Ueland, 2017, Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test, Eur J Endocrinol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataSalivary cortisol and cortisone concentrations were measured by liquid chromatography-tandem mass spectrometry with coefficients of variation of 6% for cortisol and 7% for cortisone.
“The coefficients of variation were 6% for cortisol at concentrations between 2.2 and 18.4 nmol/L and 7% for cortisone at concentrations between 4.7 and 26.8 nmol/L.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premiseown dataThe upper limit of normal for UFC used in this study was 136 nmol/L.
“The upper limit of normal for UFC was 136 nmol/L.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn general, p-cortisol following DST <50 nmol/L was considered to exclude hypercortisolism.
“In general, p-cortisol following DST <50 nmol/L was considered to exclude hypercortisolism, while values >138 nmol/L were considered to be highly suggestive for hypercortisolism (1, 2).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [1] Fassnacht, 2016, Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors, Eur J Endocrinol source
Not checked in the free run.
- cites [2] Nieman, 2008, The diagnosis of cushing's syndrome: An endocrine society clinical practice guideline, J Clin Endocrinol Metab source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductcitationContamination with exogenous hydrocortisone or blood in salivary samples was determined by calculating the salivary-cortisol:cortisone ratio, and samples with a ratio over the 97.5 percentile for the whole cohort (1.0) were considered contaminated.
“Contamination with exogenous hydrocortisone, or blood, in the salivary samples was determined by calculating the salivary-cortisol:cortisone ratio as previously described (17). Samples with a ratio over the 97.5 percentile for the whole cohort (1.0) were considered to be contaminated.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationFor patients with adrenal incidentaloma, DST is the most commonly recommended first-line screening test for ACS.
“For patients with adrenal incidentaloma, DST is the most commonly recommended first-line screening test for ACS (1–5).”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [1] Fassnacht, 2016, Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors, Eur J Endocrinol source
Not checked in the free run.
- cites [2] Nieman, 2008, The diagnosis of cushing's syndrome: An endocrine society clinical practice guideline, J Clin Endocrinol Metab source
Not checked in the free run.
- cites [3] Yanase, 2018, New diagnostic criteria of adrenal subclinical cushing's syndrome: Opinion from the Japan endocrine society, Endocr J source
Not checked in the free run.
- cites [4] Zeiger, 2009, American Association of clinical endocrinologists and American association of endocrine surgeons medical guidelines for the management of adrenal incidentalomas: executive summary of recommendations, Endocr Pract source
Not checked in the free run.
- cites [5] Lee, 2017, Clinical guidelines for the management of adrenal incidentaloma, Endocrinol Metab (Seoul) source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premiseown dataThe lower limit of normal for p-ACTH used in this study was 2.0 pmol/L.
“The lower limit of normal for p-ACTH was 2.0 pmol/L.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningSa-cortisol and/or Sa-cortisone following DST are promising diagnostic tools in patients with adrenal incidentaloma as well as patients with suspected CS.
“Thus, Sa-cortisol and/or Sa-cortisone following DST are promising diagnostic tools in patients with adrenal incidentaloma as well as patients with suspected CS.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Study design and conductnone givenMeasuring Sa-cortisol and Sa-cortisone simultaneously enables detection of contamination by exogenous hydrocortisone in the samples.
“In addition, measuring Sa-cortisol and Sa-cortisone simultaneously enables detection of contamination by exogenous hydrocortisone in the samples.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductreasoningElevated P-cortisol following DST is often required for diagnosing ACS, which may have contributed to the high sensitivity of this test.
“In addition, elevated P-cortisol following DST is often required for diagnosing ACS, which inevitably may have contributed to the high sensitivity of this test.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningLNSC does not by itself seem to be sufficiently sensitive to screen patients with suspected hypercortisolism, neither in patients with adrenal incidentalomas, nor in patients with suspected CS.
“In conclusion, LNSC does not by itself seem to be sufficiently sensitive to screen patients with suspected hypercortisolism, neither in patients with adrenal incidentalomas, nor in patients with suspected CS.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThere is no international consensus on how ACS in patients with adrenal incidentalomas should be diagnosed, and different recommendations have been provided.
“Currently, there is no international consensus on how ACS in patients with adrenal incidentalomas should be diagnosed, and different recommendations have been provided (1–5, 21–23).”
Quote in the paperNot a substantial claim0 of 8 sources checked- cites [1] Fassnacht, 2016, Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors, Eur J Endocrinol source
Not checked in the free run.
- cites [2] Nieman, 2008, The diagnosis of cushing's syndrome: An endocrine society clinical practice guideline, J Clin Endocrinol Metab source
Not checked in the free run.
- cites [3] Yanase, 2018, New diagnostic criteria of adrenal subclinical cushing's syndrome: Opinion from the Japan endocrine society, Endocr J source
Not checked in the free run.
- cites [4] Zeiger, 2009, American Association of clinical endocrinologists and American association of endocrine surgeons medical guidelines for the management of adrenal incidentalomas: executive summary of recommendations, Endocr Pract source
Not checked in the free run.
- cites [5] Lee, 2017, Clinical guidelines for the management of adrenal incidentaloma, Endocrinol Metab (Seoul) source
Not checked in the free run.
- cites [21] Grumbach, 2003, Management of the clinically inapparent adrenal mass ("incidentaloma"), Ann Intern Med source
Not checked in the free run.
- cites [22] Fleseriu, 2021, Consensus on diagnosis and management of cushing's disease: a guideline update, Lancet Diabetes Endocrinol source
Not checked in the free run.
- cites [23] Tabarin, 2022, Consensus statement by the French society of endocrinology (SFE) and French society of pediatric endocrinology & diabetology (SFEDP) on diagnosis of cushing's syndrome, Ann Endocrinol (Paris) source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationP-cortisol >138 nmol/L following DST has been suggested for diagnosis of ACS by the National Institute of Health.
“P-cortisol >138 nmol/L following DST has been suggested for diagnosis of ACS by the National Institute of Health (21).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Grumbach, 2003, Management of the clinically inapparent adrenal mass ("incidentaloma"), Ann Intern Med source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn a recent meta-analysis including 139 studies, the accuracy of laboratory tests for CS was investigated.
“In a recent meta-analysis including 139 studies, the accuracy of laboratory tests for CS was investigated (24).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Galm, 2020, Accuracy of laboratory tests for the diagnosis of cushing syndrome, J Clin Endocrinol Metab source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductreasoningBoth salivary cortisol and cortisone were measured, enabling calculation of the cortisol:cortisone ratio and evaluation if the samples were contaminated with exogenous cortisol (hydrocortisone).
“Furthermore, both salivary cortisol and cortisone were measured, enabling calculation of the cortisol:cortisone ratio and evaluation if the samples were contaminated with exogenous cortisol (hydrocortisone).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn that study, 13 of 25 patients with ACS had elevated post-DST Sa-cortisol and 23 of 25 had elevated Sa-cortisone, with 90% and 82% specificity, respectively.
“In that study, 13 of 25 patients with ACS had elevated post-DST Sa-cortisol and 23 of 25 had elevated Sa-cortisone, with 90% and 82% specificity, respectively.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Ueland, 2017, Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test, Eur J Endocrinol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningDue to the retrospective design, the diagnostic criteria for ACS was not predefined.
“Also, due to the retrospective design, the diagnostic criteria for ACS was not predefined.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataSa-cortisone at 11 p.m. and salivary cortisol and cortisone following DST seem to be promising tests in the same context.
“However, Sa-cortisone at 11 p.m. and salivary cortisol and cortisone following DST seem to be promising tests in the same context.”
Quote in the paperSubstantial claim- Rests on an assumption: The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenP-dexamethasone was not measured in our study.
“Finally, P-dexamethasone, analysed together with P-cortisol in association with DST, in order to decrease the number of false positive results (18), was not measured in our study.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Ueland, 2017, Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test, Eur J Endocrinol source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductreasoningThe diagnosis was based on clinical findings and results from different cortisol measurements, i.e., a real-life assessment made by several physicians responsible for each patient.
“Instead, the diagnosis was based on clinical findings and results from the different cortisol measurement, i.e., a real-life assessment made by several physicians responsible for each patient.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSa-cortisol and Sa-cortisone at 8 a.m. following DST has only been studied once before in the context of screening for ACS.
“Sa-cortisol and Sa-cortisone at 8 a.m. following DST has to our knowledge only been studied once before in the context of screening for ACS (18).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Ueland, 2017, Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test, Eur J Endocrinol source
Not checked in the free run.
May combine two claims.
PremisecitationAnalysis of Sa-cortisol and Sa-cortisone following DST has been used in two previous studies to screen patients with suspected CS, both showing high sensitivity (95-100%) and specificity (80-95%).
“Analysis of Sa-cortisol and Sa-cortisone following DST has also been used in two previous studies to screen patients with suspected CS, both showing a high sensitivity (95-100%) and specificity (80-95%) (17, 18), in agreement with our findings.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17] Backlund, 2020, Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in cushing's syndrome, Eur J Endocrinol source
Not checked in the free run.
- cites [18] Ueland, 2017, Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test, Eur J Endocrinol source
Not checked in the free run.
May combine two claims.
PremisecitationIn that meta-analysis, sensitivity was high for all tests, lowest for UFC (94%) and highest for DST (99%).
“The sensitivity was high for all tests, lowest for UFC (94%) and highest for DST (99%).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] Galm, 2020, Accuracy of laboratory tests for the diagnosis of cushing syndrome, J Clin Endocrinol Metab source
Not checked in the free run.
The paper relies on this without support.
The real-life clinical assessment made by the treating endocrinologist correctly classifies patients with adrenal incidentaloma as having ACS or non-functioning adrenal incidentaloma.
“Currently, there is no consensus regarding diagnostic criteria for ACS (6). Therefore, in this study, no predefined diagnostic criteria were used. Instead, the diagnosis was provided through a real-life clinical assessment made by the treating endocrinologist.”
The paper relies on this without support.
The clinical diagnosis of ACS/CS made by treating clinicians is a valid reference standard for evaluating the diagnostic accuracy of salivary cortisol and cortisone.
“Instead, the diagnosis was based on clinical findings and results from the different cortisol measurement, i.e., a real-life assessment made by several physicians responsible for each patient.”
The paper relies on this without support.
LC-MS/MS is more accurate than other analytical methods used to analyze steroids.
“Another strength is that the salivary samples were analyzed using LC-MS/MS, which is more accurate than other analytical methods used to analyze steroids.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The authors and others have shown that salivary cortisol and cortisone after DST have high diagnostic accuracy for Cushing's syndrome, but many methods lack an established diagnostic cut-off.
“We and others have shown salivary cortisol and cortisone after DST to have high diagnostic accuracy for CS, but many methods lack an established cut-off for diagnosis [2-5, 41, 42].”
From Salivary cortisol and cortisone in diagnosis of Cushing's syndrome: a comparison of six different analytical methods (2023) · cites this paper as [42]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
LNSC-positive counts differ between analyses
MajorTable 1 reports 15 patients with elevated LNSC across the two adrenal-incidentaloma groups (11 plus 4). The later division of the same 155 patients by post-DST cortisol reports only 13 (11 plus 2).
“| LNSC >3 nmol/L | 11 (8)** | 4 (40) | 0.009 | 40% | 92% |”
“LNSC was >3 nmol/L in 11 (8%), late-night Sa-cortisone >15 nmol/L in 14 (10%), salivary cortisol at 8 a.m. following DST >1 nmol/L in 9 (6%) and salivary cortisone at 8 a.m. following DST >3 nmol/L in 32 (23%). In comparison, of patients with P-cortisol >138 nmol/L after DST (n=15), two (13%) had LNSC >3 nmol/L”
Women's percentage does not match the stated count
MinorThe stated 45 women among 54 patients is 83%, not 87%.
Reported 87 · recomputed 83.333333
“In total, 54 patients, 45 women (87%) and 9 men (13%), with suspected CS were included in the analysis.”
Table 4 defines an adrenal-adenoma diagnosis as pituitary
MinorThe text says two CS patients had cortisol-producing adrenal adenomas, but the note defining their Table 4 diagnosis label, CPAA, calls it a pituitary adenoma.
“two with cortisol-producing adrenal adenoma”
“CPAA, Cortisol producing pituitary adenoma”
Women's total differs between the text and Table 3
MinorTable 3 lists 40 women without CS and 6 with CS, totaling 46 rather than the 45 stated in the text.
Reported 45 · recomputed 46
“In total, 54 patients, 45 women (87%) and 9 men (13%), with suspected CS were included in the analysis.”
The cited LNSC threshold reverses direction
MinorThe discussion describes the cited test as salivary cortisol below 2.8 nmol/L, whereas Table 5 describes it as LNSC above 2.8 nmol/L.
“the sensitivity of Sa-cortisol <2.8 nmol/L at 11 p.m. was 31%, and the specificity was 83%”
“LNSC >2.8 nmol/l had 31% sensitivity and 83% specificity for predicting ACS”
Cites
The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.
Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., Stewart, P. M., & Montori, V. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0125 · Cited by 2,718 · see citing works
Fassnacht, M., Arlt, W., Bancos, I., Dralle, H., Newell-Price, J., Sahdev, A., Tabarin, A., Terzolo, M., Tsagarakis, S., & Dekkers, O. M. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0467 · Cited by 1,566 · see citing works
Consensus on diagnosis and management of Cushing's disease: a guideline update
Fleseriu, M., Auchus, R., Bancos, I., Ben-Shlomo, A., Bertherat, J., Biermasz, N. R., Boguszewski, C. L., Bronstein, M. D., Buchfelder, M., Carmichael, J. D., et al. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00235-7 · Cited by 953 · see citing works
Management of the clinically inapparent adrenal mass ("incidentaloma")
Grumbach, M. M., Biller, B. M. K., Braunstein, G. D., Campbell, K. K., Carney, J. A., Godley, P. A., Harris, E. L., Lee, J. K. T., Oertel, Y. C., Posner, M. C., et al. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-138-5-200303040-00013 · Cited by 945 · cited 2× · see citing works
“TYPE Original Research PUBLISHED 23 November 2022 DOI 10.3389/fendo.2022.1028804 The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism Vendela Berndt1,2, Per Dahlqvist3, Jennie de Verdier4, Henrik Ryberg2,4 and Oskar Ragnarsson1,2* 1Department of Endocrinology, Sa…”
MethodInfluentialSherlock, M., Scarsbrook, A., Abbas, A., Fraser, S., Limumpornpetch, P., Dineen, R., & Stewart, P. M. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa008 · Cited by 347 · cited 5× · see citing works
“, a “false positive test”, in agreement with previous rapports (6).”
BackgroundResultInfluentialZeiger, M. A., Thompson, G. B., Duh, Q.-Y., Hamrahian, A. H., Angelos, P., Elaraj, D., Fishman, E., Kharlip, J., Hamrahian, A. H., Garber, J. R., et al. (2009) · Endocrine Practice · doi:10.4158/ep.15.5.450 · Cited by 333 · see citing works
Late-night salivary cortisol as a screening test for cushing's syndrome
Raff, H. (1998) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.8.2681 · Cited by 194 · see citing works
Clinical guidelines for the management of adrenal incidentaloma
Lee, J.-M., Kim, M. K., Ko, S.-H., Koh, J.-M., Kim, B.-Y., Kim, S. W., Kim, S.-K., Kim, H. J., Ryu, O.-H., Park, J., et al. (2017) · Endocrinology and Metabolism · doi:10.3803/enm.2017.32.2.200 · Cited by 147 · see citing works
Masserini, B., Morelli, V., Bergamaschi, S., Ermetici, F., Eller-Vainicher, C., Barbieri, A. M., Maffini, M. A., Scillitani, A., Ambrosi, B., Beck-Peccoz, P., et al. (2009) · European Journal of Endocrinology · doi:10.1530/eje-08-0485 · Cited by 106 · cited 1× · see citing works
“Instead, LNSC may be used in combination with other tests to confirm the disorder (11).”
BackgroundAccuracy of laboratory tests for the diagnosis of Cushing syndrome
Galm, B. P., Qiao, N., Klibanski, A., Biller, B. M. K., & Tritos, N. A. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa105 · Cited by 100 · cited 1× · see citing works
“In a recent meta-analysis including 139 studies, the accuracy of laboratory tests for CS was investigated (24).”
MethodUeland, G. Å., Methlie, P., Kellmann, R., Bjørgaas, M., Åsvold, B. O., Thorstensen, K., Kelp, O., Thordarson, H. B., Mellgren, G., Løvås, K., et al. (2017) · European Journal of Endocrinology · doi:10.1530/eje-17-0078 · Cited by 94 · cited 4× · see citing works
“following DST has to our knowledge only been studied once before in the context of screening for ACS (18).”
BackgroundMethodResultInfluentialYanase, T., Oki, Y., Katabami, T., Otsuki, M., Kageyama, K., Tanaka, T., Kawate, H., Tanabe, M., Doi, M., Akehi, Y., et al. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej17-0456 · Cited by 90 · see citing works
Tabarin, A., Assié, G., Barat, P., Bonnet, F., Bonneville, J. F., Borson-Chazot, F., Bouligand, J., Boulin, A., Brue, T., Caron, P., et al. (2022) · Annales d Endocrinologie · doi:10.1016/j.ando.2022.02.001 · Cited by 59 · see citing works
Palmieri, S., Morelli, V, Polledri, E., Fustinoni, S., Mercadante, R., Olgiati, L., Eller Vainicher, C., Cairoli, E., Zhukouskaya, V. V., Beck-Peccoz, P., et al. (2013) · European Journal of Endocrinology · doi:10.1530/eje-12-0803 · Cited by 57 · cited 2× · see citing works
“To our knowledge, LC-MS/MS has only been used three times before for measuring LNSC in patients with adrenal incidentaloma (12, 15, 16).”
BackgroundMethodBäcklund, N., Brattsand, G., Israelsson, M., Ragnarsson, O., Burman, P., Edén Engström, B., Høybye, C., Berinder, K., Wahlberg, J., Olsson, T., et al. (2020) · European Journal of Endocrinology · doi:10.1530/eje-19-0872 · Cited by 46 · cited 6× · see citing works
“The saliva samples were collected at home using Salivette® Cortisol tubes (Sarstedt, Nümbrecht, Germany) after oral and written instructions on how to properly collect the saliva had been provided (17).”
BackgroundMethodResultInfluentialSelf-citationCeccato, F., Antonelli, G., Frigo, A. C., Regazzo, D., Plebani, M., Boscaro, M., & Scaroni, C. (2017) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0644-8 · Cited by 44 · see citing works
Diagnostic testing of autonomous cortisol secretion in adrenal incidentalomas
Ueland, G. Å., Grinde, T., Methlie, P., Kelp, O., Løvås, K., & Husebye, E. S. (2020) · Endocrine Connections · doi:10.1530/ec-20-0419 · Cited by 40 · cited 2× · see citing works
“Similar results were found in a study from Norway on 165 patients with adrenal incidentaloma (15), and a study from Italy on 106 patients (16).”
MethodResultDaily salivary cortisol and cortisone rhythm in patients with adrenal incidentaloma
Ceccato, F., Barbot, M., Albiger, N., Antonelli, G., Zilio, M., Todeschini, M., Regazzo, D., Plebani, M., Lacognata, C., Iacobone, M., et al. (2018) · Endocrine · doi:10.1007/s12020-017-1421-3 · Cited by 38 · cited 2× · see citing works
“Similar results were found in a study from Norway on 165 patients with adrenal incidentaloma (15), and a study from Italy on 106 patients (16).”
MethodResultKannankeril, J., Carroll, T., Findling, J. W., Javorsky, B., Gunsolus, I. L., Phillips, J., & Raff, H. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa107 · Cited by 36 · cited 2× · see citing works
“Late-night Sa-cortisone >15 nmol/L 13 (9)** 9 (90) <0.”
Mészáros, K., Karvaly, G., Márta, Z., Magda, B., Tőke, J., Szücs, N., Tóth, M., Rácz, K., & Patócs, A. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-017-0743-6 · Cited by 27 · cited 1× · see citing works
“methods with lower analytical specificity than LC-MS/MS due to a risk of cross-reactions between cortisol and other steroid metabolites (19, 20).”
MethodPonzetto, F., Settanni, F., Parasiliti-Caprino, M., Rumbolo, F., Nonnato, A., Ricciardo, M., Amante, E., Priolo, G., Vitali, S., Anfossi, L., et al. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01388-1 · Cited by 25 · see citing works
Araujo-Castro, M., García Cano, A., Jiménez Mendiguchía, L., Escobar-Morreale, H. F., & Valderrábano, P. (2021) · Scientific Reports · doi:10.1038/s41598-021-00011-4 · Cited by 24 · see citing works
Israelsson, M., Brattsand, R., & Brattsand, G. (2018) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563217724178 · Cited by 21 · see citing works
Mohamed, R. S., Abuelgasim, B., Barker, S., Prabhudev, H., Martin, N. M., Meeran, K., Williams, E. L., Darch, S., Matthew, W., Tan, T., et al. (2022) · Endocrine Connections · doi:10.1530/ec-22-0050 · Cited by 18 · cited 2× · see citing works
“Post-DST Sa-cortisone >5 nmol/L 11 (8)*** 6 (60) <0.”
Background
Flagged first, then by citations
1 of the 25 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Lanfermeijer, M., van Winden, L. J., Starreveld, D. E. J., Razab-Sekh, S., van Faassen, M. H. J. R., Bleiker, E. M. A., & van Rossum, H. H. (2024) · Analytical Biochemistry · doi:10.1016/j.ab.2024.115496 · Cited by 14 · see citing works
Trandafir, A.-I., & Carşote, M. (2025) · Biomedicines · doi:10.3390/biomedicines13092169 · Cited by 10 · see citing works
“…or low-normal basal morning plasma adrenocorticotropic hormone (ACTH), an elevated midnight serum cortisol or late-night salivary cortisol (LNSC), and/or an increased urinary free cortisol (UFC), which otherwise are not currently regarded as standard diagnosis criteria, as opposite to DST [9,10].”
Bäcklund, N., Brattsand, G., Lundstedt, S., Aardal, E., Bartuseviciene, I., Berinder, K., Höybye, C., Burman, P., Edén Engström, B., Isaksson, A., et al. (2023) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2023-0141 · Cited by 9 · see citing works
Self-citationMordaunt, M., Heald, A. H., Majeed, W., Kochhar, R. S., Syed, A. A., Mudaliar, R. N., Alshames, R., Hanna, F., Marshall, D., Keevil, B. G., et al. (2025) · Clinical Endocrinology · doi:10.1111/cen.15233 · Cited by 6 · see citing works
Fertility and pregnancy in adrenal insufficiency
Green, D., Dineen, R., O’Reilly, M., & Sherlock, M. (2023) · Endocrine Connections · doi:10.1530/ec-23-0088 · Cited by 8 · see citing works
“Salivary cortisol/cortisone has emerged as an alternative tool in the assessment of cortisol exposure and is used as a diagnostic tool in Cushing’s disease ( 111 ) and more recently investigated in the diagnosis of adrenal insufficiency ( 112 ).”
MethodNeoplastic hypercortisolism: Cut-off values for late-night salivary cortisol & cortisone
Koops, K., Bisschop, P. H. L. T., Heijboer, A. C., & Hillebrand, J. J. (2025) · Clinica Chimica Acta · doi:10.1016/j.cca.2025.120310 · Cited by 2 · see citing works
Bilateral Adrenal Nodules Presenting With Mild Autonomous Cortisol Secretion
Sandooja, R., Hamidi, O., Zhang, C. D., Dogra, P., Athimulam, S., Rahimi, L., Villavicencio, C. A., Chacko, S. R., Young, W. F., & Bancos, I. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.06.019 · Cited by 2 · see citing works
Aagaard, L. S., Krogh, J., Perlman, S., Klose, M., & Andreassen, M. (2025) · Clinical Endocrinology · doi:10.1111/cen.70020 · Cited by 1 · see citing works
Yan, S., Liu, L., Zhao, Z., & Liu, L. (2026) · Scientific Reports · doi:10.1038/s41598-026-60002-1 · Cited by 2 · see citing works
“Salivary cortisol samples were collected between 2:00 PM and 5:00 PM 29 .”
Bravi, C. A. (2025) · Urologic Clinics of North America · doi:10.1016/j.ucl.2025.01.002 · Cited by 1 · see citing works
New tools for the diagnosis of hypercortisolism
Zhao, Q., Sima, O.-C., Estapé, M., Casals, G., & Hanzu, F. A. (2026) · Vitamins and hormones · doi:10.1016/bs.vh.2026.02.007
Cut-off values of urinary free cortisol and cortisone for diagnosing neoplastic hypercortisolism
Koops, K., Hillebrand, J. J., Heijboer, A. C., & Bisschop, P. H. L. T. (2026) · Clinica Chimica Acta · doi:10.1016/j.cca.2026.121107
Koops, K., Heijboer, A. C., Bisschop, P. H. L. T., & Hillebrand, J. J. (2026) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgag249
- Authors
- Berndt, V., Dahlqvist, P., de Verdier, J., Ryberg, H., & Ragnarsson, O.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Umeå University (SE)
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2022-11-23
- Volume
- 13
- Pages
- 1028804-1028804
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC9728582
- OpenAlex
- W4309707432
- Semantic Scholar
- b1a8572a73c5fef64aa092bd9a3966bc585bab8f
- Cited by
- 15
- References
- 25
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 1 · 2023: 2
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sahlgrenska Universitetssjukhuset
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- salivary cortisol, salivary cortisone, hypercortisolism, Cushing's syndrome, adrenal incidentaloma, autonomous cortisol secretion, dexamethasone suppression test, diagnostic accuracy
- MeSH terms
- Adrenal Gland Neoplasms, Cortisone, Cushing Syndrome, Humans, Hydrocortisone, Retrospective Studies
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Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
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