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Hershel Raff - One of the best experts on this subject based on the ideXlab platform.
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bedtime Salivary Cortisol and cortisone by lc ms ms in healthy adult subjects evaluation of sampling time
Journal of the Endocrine Society, 2019Co-Authors: Hershel Raff, Jonathan PhillipsAbstract:The measurement of late-night Salivary Cortisol is a mainstay in the diagnosis of Cushing syndrome. Furthermore, the measurement of Salivary Cortisol is useful in assessing the Cortisol awakening response. Because the Salivary glands express 11-β-hydroxysteroid dehydrogenase, the measurement of Salivary cortisone may improve the performance of Salivary corticosteroid measurements. We measured Salivary Cortisol by enzyme immunoassay (EIA) and Salivary Cortisol and cortisone by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in only 50 µL of saliva sampled from 54 healthy subjects (aged 20 to 64 years). We allowed patients to sample at their normal bedtime (2025 to 2400 hours) to answer a common question as to whether sampling at the normal bedtime is equivalent to the standard required sampling at 2300 to 2400 hours. We found that the Salivary Cortisol and cortisone results by LC-MS/MS correlated well with Salivary Cortisol measured with the US Food and Drug Administration-cleared EIA. Furthermore, the upper limit of normal of Salivary Cortisol by EIA for bedtime samples was lower than the previously published upper limit of normal with sampling required at 2300 to 2400 hours. There were no significant effects of age or sex on any of the Salivary steroid measurements. We conclude that (i) Salivary Cortisol and cortisone can be reliably measured by LC-MS/MS in small volumes of saliva and (ii) that patients can be evaluated using saliva sampled at their normal bedtime, rather than being required to stay awake until 2300 to 2400 hours.
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cushing s syndrome diagnosis and surveillance using Salivary Cortisol
Pituitary, 2012Co-Authors: Hershel RaffAbstract:This short review summarizes the use of late-night Salivary Cortisol measurement in the diagnosis of Cushing’s syndrome, in the evaluation of patients with adrenal incidentalomas, and in monitoring of post-operative patients, with a focus on the different assay methodologies currently in common use. The focus is on recent studies identified by literature searches using Ovid Medline and Google Scholar as well as analysis of several recent review articles on the topic. Measurement of late night Salivary Cortisol (LNSC) has an excellent sensitivity and specificity for the diagnosis of Cushing’s syndrome regardless of the assay methodology used. Immunoassays have the advantage of simplicity, low cost, and small sample volume requirement, while liquid chromatography-tandem mass spectrometry has the advantage of a high specificity for Cortisol and the ability to measure cortisone. The overnight dexamethasone suppression test appears to be superior to LNSC measurement in the evaluation of patients with adrenal incidentalomas. LNSC measurement is an excellent approach to monitor post-operative Cushing’s disease patients for surgical failure or recurrence. Salivary Cortisol is most useful as the initial test when Cushing’s syndrome is suspected and for periodic patient monitoring after pituitary surgery for Cushing’s disease.
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late night Salivary Cortisol for the diagnosis of cushing syndrome a meta analysis
Endocrine Practice, 2009Co-Authors: Ty B Carroll, Hershel Raff, James W FindlingAbstract:Objective: To report a meta-analysis of late-night Salivary Cortisol testing for the diagnosis of Cushing syndrome.Methods: MEDLINE and EMBASE computer databases were searched to identify relevant ...
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cosyntropin stimulated Salivary Cortisol in hospitalized patients with hypoproteinemia
Endocrine, 2008Co-Authors: Hershel Raff, Scott Brock, James W FindlingAbstract:Analysis of adrenocortical function in acutely ill, hospitalized patients can be challenging due to changes in plasma binding proteins. This study used dynamic testing of Salivary Cortisol levels to evaluate adrenal function in hospitalized patients with low/low-normal plasma protein concentration in whom adrenal insufficiency was suspected. Twenty-eight patients with low serum albumin and proteins hospitalized for acute illness were evaluated for decreased adrenocortical function because of clinical presentations suspicious for adrenal insufficiency. Baseline and post cosyntropin-stimulated levels of serum total and Salivary Cortisol levels were assessed. Data were gathered by a retrospective analysis of medical records. Eight patients had normal peak serum total and Salivary Cortisol responses, consistent with intact adrenocortical function. Five patients had abnormal peak serum total and Salivary Cortisol responses indicating decreased adrenocortical function. Fifteen patients had subnormal peak serum total Cortisol, but normal peak Salivary Cortisol responses indicating normal adrenal function. Salivary Cortisol testing can identify hospitalized patients with apparently intact adrenal function in whom low serum protein confounded interpretation of serum total Cortisol measurements. Salivary Cortisol is a clinically useful surrogate for serum free Cortisol in dynamic testing of adrenocortical function.
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new enzyme immunoassay for Salivary Cortisol
Clinical Chemistry, 2003Co-Authors: Hershel Raff, Peter J Homar, David P SkonerAbstract:The measurement of Salivary Cortisol is emerging as the simplest approach in the diagnosis of Cushing syndrome (1)(2)(3). One of the problems with previous methods is the lack of a Food and Drug Administration (FDA)-cleared method. We have evaluated an enzyme immunoassay (EIA) for Salivary Cortisol marketed by Salimetrics (State College, PA) and recently cleared by the FDA for in vitro diagnostic use. We compared the new EIA with our modified RIA (2) in 147 samples. The first set of samples (n = 44) was collected at 2300 and 0700 from a group of apparently healthy adult individuals (n = 22; age range, 25–60 years; 11 females and 11 males). The second set of samples (n = 30) was collected at 2300 by patients (n = 30; age range, 12–84 years; 22 females and 8 males) to screen for Cushing syndrome. The third set of samples (n = 73) was collected between 0600 and 1000 from participants (n = 42; age range, 6–14 years; 21 females and 21 males) enrolled in a study of allergic rhinitis. The study was approved by the appropriate Institutional Review Boards, and consent was obtained. Saliva was …
James W Findling - One of the best experts on this subject based on the ideXlab platform.
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late night Salivary Cortisol for the diagnosis of cushing syndrome a meta analysis
Endocrine Practice, 2009Co-Authors: Ty B Carroll, Hershel Raff, James W FindlingAbstract:Objective: To report a meta-analysis of late-night Salivary Cortisol testing for the diagnosis of Cushing syndrome.Methods: MEDLINE and EMBASE computer databases were searched to identify relevant ...
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cosyntropin stimulated Salivary Cortisol in hospitalized patients with hypoproteinemia
Endocrine, 2008Co-Authors: Hershel Raff, Scott Brock, James W FindlingAbstract:Analysis of adrenocortical function in acutely ill, hospitalized patients can be challenging due to changes in plasma binding proteins. This study used dynamic testing of Salivary Cortisol levels to evaluate adrenal function in hospitalized patients with low/low-normal plasma protein concentration in whom adrenal insufficiency was suspected. Twenty-eight patients with low serum albumin and proteins hospitalized for acute illness were evaluated for decreased adrenocortical function because of clinical presentations suspicious for adrenal insufficiency. Baseline and post cosyntropin-stimulated levels of serum total and Salivary Cortisol levels were assessed. Data were gathered by a retrospective analysis of medical records. Eight patients had normal peak serum total and Salivary Cortisol responses, consistent with intact adrenocortical function. Five patients had abnormal peak serum total and Salivary Cortisol responses indicating decreased adrenocortical function. Fifteen patients had subnormal peak serum total Cortisol, but normal peak Salivary Cortisol responses indicating normal adrenal function. Salivary Cortisol testing can identify hospitalized patients with apparently intact adrenal function in whom low serum protein confounded interpretation of serum total Cortisol measurements. Salivary Cortisol is a clinically useful surrogate for serum free Cortisol in dynamic testing of adrenocortical function.
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late night Salivary Cortisol as a screening test for cushing s syndrome
The Journal of Clinical Endocrinology and Metabolism, 1998Co-Authors: Hershel Raff, Jonathan L Raff, James W FindlingAbstract:The clinical features of Cushing's syndrome (such as obesity, hypertension, and diabetes) are commonly encountered in clinical practice. Patients with Cushing's syndrome have been identified by an abnormal low-dose dexamethasone suppression test, elevated urine free Cortisol (UFC), an absence of diurnal rhythm of plasma Cortisol, or an elevated late-night plasma Cortisol. Because the concentration of Cortisol in the saliva is in equilibrium with the free (active) Cortisol in the plasma, measurement of Salivary Cortisol in the evening (nadir) and morning (peak) may be a simple and convenient screening test for Cushing's syndrome. The purpose of this study was to evaluate the usefulness of the measurement of late-night and morning Salivary Cortisol in the diagnosis of Cushing's syndrome. We studied 73 normal subjects and 78 patients referred for the diagnosis of Cushing's syndrome. Salivary Cortisol was measured at 2300 h and 0700 h using a simple, commercially-available saliva collection device and a modification of a standard Cortisol RIA. In addition, 24-h UFC was measured within 1 month of saliva sampling. Patients with proven Cushing's syndrome (N = 39) had significantly elevated 2300-h Salivary Cortisol (24.0 +/- 4.5 nmol/L), as compared with normal subjects (1.2 +/- 0.1 nmol/L) or with patients referred with the clinical features of hyperCortisolism in whom the diagnosis was excluded or not firmly established (1.6 +/- 0.2 nmol/L; N = 39). Three of 39 patients with proven Cushing's had 2300-h Salivary Cortisol less than the calculated upper limit of the reference range (3.6 nmol/L), yielding a sensitivity of 92%; one of these 3 patients had intermittent hyperCortisolism, and one had an abnormal diurnal rhythm (Salivary Cortisol 0700-h to 2300-h ratio <2). An elevated 2300-h Salivary Cortisol and/or an elevated UFC identified all 39 patients with proven Cushing's syndrome (100% sensitivity). Salivary Cortisol measured at 0700 h demonstrated significant overlap between groups, even though it was significantly elevated in patients with proven Cushing's syndrome (23.0 +/- 4.2 nmol/L), as compared with normal subjects (14.5 +/- 0.8 nmol/L) or with patients in whom Cushing's was excluded or not firmly established (15.3 +/- 1.5 nmol/L). Late-night Salivary Cortisol measurement is a simple and reliable screening test for spontaneous Cushing's syndrome. In addition, late-night Salivary Cortisol measurements may simplify the evaluation of suspected intermittent hyperCortisolism, and they may facilitate the screening of large high-risk populations (e.g. patients with diabetes mellitus).
Filippo Ceccato - One of the best experts on this subject based on the ideXlab platform.
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improved Salivary Cortisol rhythm with dual release hydrocortisone
Endocrine connections, 2018Co-Authors: Filippo Ceccato, Mattia Barbot, Corrado Betterle, Elisa Selmin, Chiara Sabbadin, Miriam Dalla Costa, Giorgia Antonelli, Mario Plebani, Marco Boscaro, Carla ScaroniAbstract:Introduction and Aim The purpose of replacement therapy in adrenal insufficiency (AI) is mimicking endogenous Cortisol levels as closely as possible: dual release hydrocortisone (DR-HC) has been introduced to replicate the circadian Cortisol rhythm. Multiple daily saliva collections could be used to assess the Cortisol rhythm during real life: our aim was to study the Salivary Cortisol profile in AI. Materials and Methods We prospectively evaluated, in an observational study, 18 adult outpatients with AI (11 primary and 7 secondary AI), switched from conventional treatment (conv-HC, 25 mg/day) to the same dose of DR-HC. We collected six samples of saliva in a day, measuring Cortisol (F) and cortisone (E) with LC-MS/MS. Forty-three matched healthy subjects served as controls. Results F levels were similar in the morning (and higher than controls) in patients treated with conv-HC or DR-HC; otherwise F levels and exposure were lower in the afternoon and evening in patients with DR-HC, achieving a Cortisol profile closer to healthy controls. Daily Cortisol exposure, measured with area under the curve, was lower with DR-HC. Morning F and E presented sensitivity and specificity >90% to diagnose AI (respectively threshold of 3 and 9.45 nmol/L). Total cholesterol and HbA1c levels reduced with DR-HC. Conclusions Salivary Cortisol daily curve could be used as a new tool to assess the Cortisol profiles in patients treated with conv-HC and DR-HC. A lower daily Cortisol exposure was achieved with DR-HC (despite the same HC dose), especially in the afternoon-evening.
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daily Salivary Cortisol and cortisone rhythm in patients with adrenal incidentaloma
Endocrine, 2018Co-Authors: Filippo Ceccato, Mattia Barbot, Marialuisa Zilio, Nora Albiger, Giorgia Antonelli, Mario Plebani, Marco Todeschini, Daniela Regazzo, Carmelo Lacognata, Maurizio IacoboneAbstract:Impaired Cortisol rhythm is a characteristic feature of Cushing’s Syndrome, nevertheless late night Salivary Cortisol (LNSC) is not suitable to detect subclinical hyperCortisolism in patients with adrenal incidentaloma (AI). We studied daily Salivary Cortisol (F) and cortisone (E) rhythm in patients with AI. Six saliva samples were collected from awakening to night in 106 patients with AI and 40 controls. F and E were measured with LC-MS/MS and daily F exposure was calculated with the area under the curve (AUC). Patients with serum Cortisol after dexamethasone suppression test (DST) > 50 nmol/L showed higher morning F (15.5 ± 14.5 vs. 8.6 ± 5.5 nmol/L, p = 0.001), suppressed corticotropin levels (76 vs. 35%, p 50 nmol/L. AUC was not correlated with urinary Cortisol levels or adenoma size. F and E levels were similar among patients with unilateral or bilateral adenoma, or considering the presence of hypertension, dyslipidemia, diabetes, or cardiovascular events. Daily Cortisol exposure, evaluated with AUC from multiple saliva collections, is increased in AI patients with serum Cortisol > 50 nmol/L after DST, especially in the morning, leading to reduced corticotropin levels. Cortisol rhythm is preserved in patients with AI, remarking that LNSC is not a screening test for subclinical hyperCortisolism.
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performance of Salivary Cortisol in the diagnosis of cushing s syndrome adrenal incidentaloma and adrenal insufficiency
European Journal of Endocrinology, 2013Co-Authors: Filippo Ceccato, Mattia Barbot, Marialuisa Zilio, Sergio Ferasin, Gianluca Occhi, Andrea Daniele, Silvia Mazzocut, Maurizio Iacobone, Corrado Betterle, Franco ManteroAbstract:Objective: Salivary Cortisol has recently been suggested for studies on the hypothalamic–pituitary– adrenal (HPA) axis. The lack of circadian rhythm is a marker of Cushing’s syndrome (CS), and some authors have reported that low Salivary Cortisol levels may be a marker of adrenal insufficiency. The aim of our study was to define the role of Salivary Cortisol in specific diagnostic settings of HPA axis disease. Subjects and methods: We analyzed morning Salivary Cortisol (MSC) and late-night Salivary Cortisol (LNSC) levels in 406 subjects: 52 patients with Cushing’s disease (CD), 13 with ectopic CS, 17 with adrenal CS, 27 with CD in remission (a mean follow-up of 66G39 months), 45 with adrenal incidentaloma, 73 assessed as having CS and then ruled out for endogenous hyperCortisolism, 75 with adrenal insufficiency, and 104 healthy subjects. Results: A LNSC value above 5.24 ng/ml differentiated CS patients from controls with high sensitivity (96.3%) and specificity (97.1%); we found higher LNSC levels in ectopic CS patients than in CD patients. We found no difference in MSC and LNSC levels between patients with CD in remission and healthy subjects. Both MSC and LNSC levels were higher in patients with adrenal incidentaloma than in healthy controls. A MSC value below 2.65 ng/ml distinguished patients with adrenal insufficiency from controls with high sensitivity (97.1%) and specificity (93.3%). Conclusions: Salivary Cortisol is a useful tool to assess endogenous Cortisol excess or adrenal insufficiency and to evaluate stable CD in remission.
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assessment of glucocorticoid therapy with Salivary Cortisol in secondary adrenal insufficiency
European Journal of Endocrinology, 2012Co-Authors: Filippo Ceccato, Sergio Ferasin, Gianluca Occhi, Franco Mantero, Nora Albiger, Giuseppe Reimondo, Anna Chiara Frigo, Massimo Terzolo, Carla ScaroniAbstract:Context: Appropriate glucocorticoid replacement therapy in adrenal insufficiency (AI) is crucial, given the risks of chronic under- or overtreatment, particularly in patients on multiple medications. Salivary sampling allows for non-invasive, stress-free Cortisol measurement. Objective: To determine whether Salivary Cortisol measurement is helpful in assessing the adequacy of glucocorticoid therapy with cortisone acetate (CA) in patients with secondary AI. Design: A prospective cohort study at the Endocrinology Unit of Padua University Hospital. Methods: Six samples of Salivary Cortisol were collected from 28 patients with secondary AI on CA treatment and from 36 healthy volunteers at fixed times of the day, and used to calculate Salivary Cortisol levels at each time point and the area under the curve (AUC) across the different sampling times. Results: Salivary Cortisol levels were lower in patients than in controls in the morning but no differences were found in the afternoon or at night before resting. Salivary Cortisol levels were higher in patients immediately following CA administration. Ten patients showed an AUC above the 97.5th percentile of controls, without clinical signs of hyperCortisolism, and Salivary Cortisol levels 90 min after each dose of CA predict the AUC. All patients had severe GH deficiency and there were no differences in Salivary Cortisol levels or AUC between patients treated or not with GH. Conclusions: Two Salivary Cortisol determinations, able to predict the daily AUC, may allow for assessing the adequacy of glucocorticoid replacement therapy in secondary AI and for identifying cases of overor undertreatment.
Christina S Chao - One of the best experts on this subject based on the ideXlab platform.
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Salivary Cortisol levels by tandem mass spectrometry during high dose acth stimulation test for adrenal insufficiency in children
Endocrine, 2020Co-Authors: Christina S Chao, Rajiv B KumarAbstract:Serum Cortisol measurements after ACTH stimulation are currently used to evaluate for adrenal insufficiency in children. We aim to determine if Salivary Cortisol measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS) can confirm or replace serum Cortisol during high dose ACTH stimulation test to improve test compliance and interpretation. We also aim to gain preliminary understanding of normal ranges of Salivary Cortisol in normal children at am, bedtime, and midnight. Children aged 6–17 years meeting study criteria and tested for adrenal insufficiency were recruited to concomitantly collect saliva and serum samples during high dose ACTH stimulation test. Normal children aged 3–18 years were recruited to collect morning, bedtime, and midnight saliva samples. Salivary Cortisol was measured using LC–MS/MS while serum Cortisol was determined by an immunoassay. Salivary Cortisol in normal children were higher at am and lower at bedtime and midnight (p value <0.0002 and <0.007, respectively). The midnight and bedtime levels were not sufficiently different (p value 0.36). Salivary Cortisol during ACTH stimulation test positively and closely correlated with serum Cortisol with 100% specificity and sensitivity when 18 µg/dL for serum and 500 ng/dL for Salivary Cortisol were used as cutoff values respectively for adrenal sufficiency. Measurement of Salivary Cortisol by LC–MS/MS is less invasive, more convenient and better time controlled in busy pediatric clinic, therefore is better suited for young children to be used during high dose ACTH stimulation test to evaluate for adrenal insufficiency and to assist interpretation of test results by serum Cortisol.
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clinical utility of an ultrasensitive late night Salivary Cortisol assay by tandem mass spectrometry
Steroids, 2018Co-Authors: Lillian R Sturmer, Christina S Chao, Dylan Dodd, Run Zhang ShiAbstract:Abstract Background Late night Salivary Cortisol measurement is a clinically important and convenient screening test for Cushing’s syndrome. Tandem mass spectrometry (LC-MS/MS) assays have superior sensitivity and specificity compared to immunoassays. Our goal was to improve a LC-MS/MS method to measure Salivary Cortisol in both adult and pediatric patients and to characterize its analytical performance by method validation and clinical performance by chart review. Methods We improved a LC-MS/MS method originally developed for urine Cortisol to measure low level Salivary Cortisol. The sample preparation was by liquid-liquid extraction using dichloromethane followed by stepwise washing with acidic, basic and neutral solutions. The assay’s analytical performance was characterized and retrospective patient chart review was conducted to evaluate the assay’s clinical diagnostic performance. Results The LC-MS/MS assay showed enhanced functional sensitivity of 10 ng/dL for Salivary Cortisol and was linear within an analytical measurement range of 10–10,000 ng/dL. Assay accuracy was within 84–120% as determined by recovery studies and correlation with a reference method. Data from healthy adult volunteers was compiled to establish the reference interval for late night Salivary Cortisol. Patient chart review determined subjects with diagnosis of Cushing’s syndrome or disease, and assay’s clinical diagnostic sensitivity of 100% and specificity of 92% when the cutoff value was 70 ng/dL. Conclusions The improved LC-MS/MS method is sensitive and specific with enhanced analytical performance and clinical diagnostic utility for screening Cushing’s syndrome. The assay may have broad clinical application due to its high sensitivity and wide dynamic range.
Franco Mantero - One of the best experts on this subject based on the ideXlab platform.
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performance of Salivary Cortisol in the diagnosis of cushing s syndrome adrenal incidentaloma and adrenal insufficiency
European Journal of Endocrinology, 2013Co-Authors: Filippo Ceccato, Mattia Barbot, Marialuisa Zilio, Sergio Ferasin, Gianluca Occhi, Andrea Daniele, Silvia Mazzocut, Maurizio Iacobone, Corrado Betterle, Franco ManteroAbstract:Objective: Salivary Cortisol has recently been suggested for studies on the hypothalamic–pituitary– adrenal (HPA) axis. The lack of circadian rhythm is a marker of Cushing’s syndrome (CS), and some authors have reported that low Salivary Cortisol levels may be a marker of adrenal insufficiency. The aim of our study was to define the role of Salivary Cortisol in specific diagnostic settings of HPA axis disease. Subjects and methods: We analyzed morning Salivary Cortisol (MSC) and late-night Salivary Cortisol (LNSC) levels in 406 subjects: 52 patients with Cushing’s disease (CD), 13 with ectopic CS, 17 with adrenal CS, 27 with CD in remission (a mean follow-up of 66G39 months), 45 with adrenal incidentaloma, 73 assessed as having CS and then ruled out for endogenous hyperCortisolism, 75 with adrenal insufficiency, and 104 healthy subjects. Results: A LNSC value above 5.24 ng/ml differentiated CS patients from controls with high sensitivity (96.3%) and specificity (97.1%); we found higher LNSC levels in ectopic CS patients than in CD patients. We found no difference in MSC and LNSC levels between patients with CD in remission and healthy subjects. Both MSC and LNSC levels were higher in patients with adrenal incidentaloma than in healthy controls. A MSC value below 2.65 ng/ml distinguished patients with adrenal insufficiency from controls with high sensitivity (97.1%) and specificity (93.3%). Conclusions: Salivary Cortisol is a useful tool to assess endogenous Cortisol excess or adrenal insufficiency and to evaluate stable CD in remission.
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assessment of glucocorticoid therapy with Salivary Cortisol in secondary adrenal insufficiency
European Journal of Endocrinology, 2012Co-Authors: Filippo Ceccato, Sergio Ferasin, Gianluca Occhi, Franco Mantero, Nora Albiger, Giuseppe Reimondo, Anna Chiara Frigo, Massimo Terzolo, Carla ScaroniAbstract:Context: Appropriate glucocorticoid replacement therapy in adrenal insufficiency (AI) is crucial, given the risks of chronic under- or overtreatment, particularly in patients on multiple medications. Salivary sampling allows for non-invasive, stress-free Cortisol measurement. Objective: To determine whether Salivary Cortisol measurement is helpful in assessing the adequacy of glucocorticoid therapy with cortisone acetate (CA) in patients with secondary AI. Design: A prospective cohort study at the Endocrinology Unit of Padua University Hospital. Methods: Six samples of Salivary Cortisol were collected from 28 patients with secondary AI on CA treatment and from 36 healthy volunteers at fixed times of the day, and used to calculate Salivary Cortisol levels at each time point and the area under the curve (AUC) across the different sampling times. Results: Salivary Cortisol levels were lower in patients than in controls in the morning but no differences were found in the afternoon or at night before resting. Salivary Cortisol levels were higher in patients immediately following CA administration. Ten patients showed an AUC above the 97.5th percentile of controls, without clinical signs of hyperCortisolism, and Salivary Cortisol levels 90 min after each dose of CA predict the AUC. All patients had severe GH deficiency and there were no differences in Salivary Cortisol levels or AUC between patients treated or not with GH. Conclusions: Two Salivary Cortisol determinations, able to predict the daily AUC, may allow for assessing the adequacy of glucocorticoid replacement therapy in secondary AI and for identifying cases of overor undertreatment.
