Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia
Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference rang...
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| Veröffentlicht in: | Clinical biochemistry 2013-10, Vol.46 (15), p.1442-1446 |
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| creator | Karpman, Matthew S. Neculau, Madalina Dias, Valerian C. Kline, Gregory A. |
| description | Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference ranges for the normal salivary cortisol levels in healthy patients and patients with adrenal insufficiency.
Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency.
We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74–0.86, p |
| doi_str_mv | 10.1016/j.clinbiochem.2013.05.004 |
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Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency.
We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74–0.86, p<0.0001). The corresponding salivary cortisol equivalent to a serum cortisol of 500nmol/L, using a linear-regression equation, was 16.7nmol/L (95% CI 13.3–20.1nmol/L, p=0.0001). A salivary cortisol of 13.3nmol/L has a specificity of 89.3% to detect abnormal HPA function. Using the upper 95% CI result of salivary cortisol 20.1 yields a sensitivity of 87.5%.
With the present assay, adrenal insufficiency may be diagnosed with reasonable confidence if a random salivary cortisol is lower than 13.3nmol/L and excluded if a random salivary cortisol is higher than 20.1nmol/L. Future studies should correlate these thresholds with clinical outcomes.
•Salivary cortisol is an accurate measure of non-protein bound cortisol.•A reference must be from a standard test of adrenal reserve like insulin hypoglycemia.•Salivary cortisol of 20.1nmol/l has almost 88% sensitivity for adrenal insufficiency.•Salivary cortisol of 13.3nmol/l has almost 90% specificity for the diagnosis.•Two cut-points for interpretation allows clinicians to make optimal use of the test.</description><identifier>ISSN: 0009-9120</identifier><identifier>EISSN: 1873-2933</identifier><identifier>DOI: 10.1016/j.clinbiochem.2013.05.004</identifier><identifier>PMID: 23684774</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adrenal function ; Adrenal Glands - metabolism ; Adrenal Glands - physiopathology ; Adrenal insufficiency ; Adrenal Insufficiency - diagnosis ; Adrenal Insufficiency - metabolism ; Adrenal Insufficiency - physiopathology ; Adult ; Aged ; Female ; Free cortisol ; Humans ; Hydrocortisone - metabolism ; Hypoglycemia - chemically induced ; Hypoglycemia - metabolism ; Hypoglycemia - physiopathology ; Hypothalamo-Hypophyseal System - metabolism ; Hypothalamo-Hypophyseal System - physiopathology ; Insulin ; Insulin hypoglycemia test ; Male ; Middle Aged ; Pituitary-Adrenal System - metabolism ; Pituitary-Adrenal System - physiopathology ; Regression Analysis ; Salivary cortisol ; Salivary Glands - chemistry ; Sensitivity and Specificity</subject><ispartof>Clinical biochemistry, 2013-10, Vol.46 (15), p.1442-1446</ispartof><rights>2013 The Canadian Society of Clinical Chemists</rights><rights>Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-844760d622bfab1df5a4e7e4579fbed2fd334adc1c2b0ea5dd3e4aa444e54ee13</citedby><cites>FETCH-LOGICAL-c377t-844760d622bfab1df5a4e7e4579fbed2fd334adc1c2b0ea5dd3e4aa444e54ee13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0009912013002002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23684774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karpman, Matthew S.</creatorcontrib><creatorcontrib>Neculau, Madalina</creatorcontrib><creatorcontrib>Dias, Valerian C.</creatorcontrib><creatorcontrib>Kline, Gregory A.</creatorcontrib><title>Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia</title><title>Clinical biochemistry</title><addtitle>Clin Biochem</addtitle><description>Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference ranges for the normal salivary cortisol levels in healthy patients and patients with adrenal insufficiency.
Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency.
We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74–0.86, p<0.0001). The corresponding salivary cortisol equivalent to a serum cortisol of 500nmol/L, using a linear-regression equation, was 16.7nmol/L (95% CI 13.3–20.1nmol/L, p=0.0001). A salivary cortisol of 13.3nmol/L has a specificity of 89.3% to detect abnormal HPA function. Using the upper 95% CI result of salivary cortisol 20.1 yields a sensitivity of 87.5%.
With the present assay, adrenal insufficiency may be diagnosed with reasonable confidence if a random salivary cortisol is lower than 13.3nmol/L and excluded if a random salivary cortisol is higher than 20.1nmol/L. Future studies should correlate these thresholds with clinical outcomes.
•Salivary cortisol is an accurate measure of non-protein bound cortisol.•A reference must be from a standard test of adrenal reserve like insulin hypoglycemia.•Salivary cortisol of 20.1nmol/l has almost 88% sensitivity for adrenal insufficiency.•Salivary cortisol of 13.3nmol/l has almost 90% specificity for the diagnosis.•Two cut-points for interpretation allows clinicians to make optimal use of the test.</description><subject>Adrenal function</subject><subject>Adrenal Glands - metabolism</subject><subject>Adrenal Glands - physiopathology</subject><subject>Adrenal insufficiency</subject><subject>Adrenal Insufficiency - diagnosis</subject><subject>Adrenal Insufficiency - metabolism</subject><subject>Adrenal Insufficiency - physiopathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Female</subject><subject>Free cortisol</subject><subject>Humans</subject><subject>Hydrocortisone - metabolism</subject><subject>Hypoglycemia - chemically induced</subject><subject>Hypoglycemia - metabolism</subject><subject>Hypoglycemia - physiopathology</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>Hypothalamo-Hypophyseal System - physiopathology</subject><subject>Insulin</subject><subject>Insulin hypoglycemia test</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pituitary-Adrenal System - metabolism</subject><subject>Pituitary-Adrenal System - physiopathology</subject><subject>Regression Analysis</subject><subject>Salivary cortisol</subject><subject>Salivary Glands - chemistry</subject><subject>Sensitivity and Specificity</subject><issn>0009-9120</issn><issn>1873-2933</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtP3DAURi1UVAbav4DMrpsEP25eSzSlBQmJDV1bjn0z45ETD3ZCNf8eowHUZVdXVzrffRxCrjgrOeP19a403k29C2aLYykYlyWrSsbghKx428hCdFJ-ISvGWFd0XLAzcp7SLrcC2vorOROybqFpYEWefuLgJjdtqLYRJ-1pmvW8JPrXzVuatHcvOh6oCXF2KXjaH-gmeFtkarI6WuqmtORj6PawDxt_MDg6_Y2cDton_P5eL8ifX7dP67vi4fH3_frmoTCyaeaiBWhqZmsh-kH33A6VBmwQqqYberRisFKCtoYb0TPUlbUSQWsAwAoQubwgP45z9zE8L5hmNbpk0Hs9YViS4iCrFqq2hYx2R9TEkFLEQe2jG_NrijP1JlXt1D9S1ZtUxSqVpebs5fuapR_RfiY_LGZgfQQwP_viMKpkHE4GrYtoZmWD-481r3J9kOw</recordid><startdate>201310</startdate><enddate>201310</enddate><creator>Karpman, Matthew S.</creator><creator>Neculau, Madalina</creator><creator>Dias, Valerian C.</creator><creator>Kline, Gregory A.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201310</creationdate><title>Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia</title><author>Karpman, Matthew S. ; Neculau, Madalina ; Dias, Valerian C. ; Kline, Gregory A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-844760d622bfab1df5a4e7e4579fbed2fd334adc1c2b0ea5dd3e4aa444e54ee13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adrenal function</topic><topic>Adrenal Glands - metabolism</topic><topic>Adrenal Glands - physiopathology</topic><topic>Adrenal insufficiency</topic><topic>Adrenal Insufficiency - diagnosis</topic><topic>Adrenal Insufficiency - metabolism</topic><topic>Adrenal Insufficiency - physiopathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Female</topic><topic>Free cortisol</topic><topic>Humans</topic><topic>Hydrocortisone - metabolism</topic><topic>Hypoglycemia - chemically induced</topic><topic>Hypoglycemia - metabolism</topic><topic>Hypoglycemia - physiopathology</topic><topic>Hypothalamo-Hypophyseal System - metabolism</topic><topic>Hypothalamo-Hypophyseal System - physiopathology</topic><topic>Insulin</topic><topic>Insulin hypoglycemia test</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pituitary-Adrenal System - metabolism</topic><topic>Pituitary-Adrenal System - physiopathology</topic><topic>Regression Analysis</topic><topic>Salivary cortisol</topic><topic>Salivary Glands - chemistry</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karpman, Matthew S.</creatorcontrib><creatorcontrib>Neculau, Madalina</creatorcontrib><creatorcontrib>Dias, Valerian C.</creatorcontrib><creatorcontrib>Kline, Gregory A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karpman, Matthew S.</au><au>Neculau, Madalina</au><au>Dias, Valerian C.</au><au>Kline, Gregory A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia</atitle><jtitle>Clinical biochemistry</jtitle><addtitle>Clin Biochem</addtitle><date>2013-10</date><risdate>2013</risdate><volume>46</volume><issue>15</issue><spage>1442</spage><epage>1446</epage><pages>1442-1446</pages><issn>0009-9120</issn><eissn>1873-2933</eissn><abstract>Insulin-induced hypoglycemia (IHT) is considered the gold standard test for evaluating the HPA axis. Serum free cortisol or its surrogate, salivary cortisol as opposed to total cortisol concentrations, offers a better reflection of the activation of HPA axis. Our study aimed to derive reference ranges for the normal salivary cortisol levels in healthy patients and patients with adrenal insufficiency.
Serum cortisol concentrations, using the gold standard of IHT, and salivary cortisol were obtained. 36 patients referred to our outpatient endocrine testing unit for evaluation of adrenal function were included in the study. Most subjects had a history of suspected hypothalamic/pituitary disease causing adrenal insufficiency.
We found a strong linear correlation between the serum and salivary cortisol concentrations in simultaneously collected samples (r=0.81, 95% CI 0.74–0.86, p<0.0001). The corresponding salivary cortisol equivalent to a serum cortisol of 500nmol/L, using a linear-regression equation, was 16.7nmol/L (95% CI 13.3–20.1nmol/L, p=0.0001). A salivary cortisol of 13.3nmol/L has a specificity of 89.3% to detect abnormal HPA function. Using the upper 95% CI result of salivary cortisol 20.1 yields a sensitivity of 87.5%.
With the present assay, adrenal insufficiency may be diagnosed with reasonable confidence if a random salivary cortisol is lower than 13.3nmol/L and excluded if a random salivary cortisol is higher than 20.1nmol/L. Future studies should correlate these thresholds with clinical outcomes.
•Salivary cortisol is an accurate measure of non-protein bound cortisol.•A reference must be from a standard test of adrenal reserve like insulin hypoglycemia.•Salivary cortisol of 20.1nmol/l has almost 88% sensitivity for adrenal insufficiency.•Salivary cortisol of 13.3nmol/l has almost 90% specificity for the diagnosis.•Two cut-points for interpretation allows clinicians to make optimal use of the test.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>23684774</pmid><doi>10.1016/j.clinbiochem.2013.05.004</doi><tpages>5</tpages></addata></record> |
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| subjects | Adrenal function Adrenal Glands - metabolism Adrenal Glands - physiopathology Adrenal insufficiency Adrenal Insufficiency - diagnosis Adrenal Insufficiency - metabolism Adrenal Insufficiency - physiopathology Adult Aged Female Free cortisol Humans Hydrocortisone - metabolism Hypoglycemia - chemically induced Hypoglycemia - metabolism Hypoglycemia - physiopathology Hypothalamo-Hypophyseal System - metabolism Hypothalamo-Hypophyseal System - physiopathology Insulin Insulin hypoglycemia test Male Middle Aged Pituitary-Adrenal System - metabolism Pituitary-Adrenal System - physiopathology Regression Analysis Salivary cortisol Salivary Glands - chemistry Sensitivity and Specificity |
| title | Defining adrenal status with salivary cortisol by gold-standard insulin hypoglycemia |
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