Salivary Profiles of 11-Oxygenated Androgens Follow a Diurnal Rhythm in Patients With Congenital Adrenal Hyperplasia
Open accessPublished version of a preprint
Abstract
CONTEXT: Several studies have highlighted the importance of the 11-oxygenated 19-carbon (11oxC19) adrenal-derived steroids as potential biomarkers for monitoring patients with 21-hydroxylase deficiency (21OHD). OBJECTIVE: To analyze circadian rhythmicity of 11oxC19 steroids in saliva profiles and evaluate their relevance as potential monitoring parameters in 21OHD. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional single-center study including 59 patients with classic 21OHD (men = 30; women = 29) and 49 body mass index- and age-matched controls (men = 19; women = 30). OUTCOME MEASURES: Salivary concentrations of the following steroids were analyzed by liquid chromatography-tandem mass spectrometry: 17-hydroxyprogesterone (17OHP), androstenedione (A4), testosterone (T), 11β-hydroxyandrostenedione (11OHA4), and 11-ketotestosterone (11KT). RESULTS: Similar to the previously described rhythmicity of 17OHP, 11OHA4 and 11KT concentrations followed a distinct diurnal rhythm in both patients and controls with highest concentrations in the early morning and declining throughout the day (11-OHA4: mean reduction of hormone concentrations between timepoint 1 and 5 (Δ mean) in male patients = 66%; male controls Δ mean = 83%; female patients Δ mean = 47%; female controls Δ mean = 86%; 11KT: male patients Δ mean = 57%; male controls Δ mean = 63%; female patients Δ mean = 50%; female controls Δ mean = 76%). Significant correlations between the area under the curve for 17OHP and 11KT (rpmale = 0.773<0.0001; rpfemale = 0.737<0.0001), and 11OHA4 (rpmale = 0.6330.0002; rpfemale = 0.5640.0014) were observed in patients but not present or reduced in controls. CONCLUSIONS: Adrenal 11oxC19 androgens are secreted following a diurnal pattern. This should be considered when evaluating their utility for monitoring treatment control.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In a recent study of patients with classic 21OHD, salivary 11OHA4 and 11KT were highest in the morning, and declined by evening.
“In a recent study of patients with classic 21OHD, salivary 11OHA4 and 11KT were highest in the morning, and declined by evening (24).”
From 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency (2021) · cites this paper as [24]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Speiser, P. W., Azziz, R., Baskin, L. S., Ghizzoni, L., Hensle, T. W., Merke, D. P., Meyer-Bahlburg, H. F. L., Miller, W. L., Montori, V. M., Oberfield, S. E., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2631 · Cited by 1,484 · see citing works
Speiser, P. W., Arlt, W., Auchus, R. J., Baskin, L. S., Conway, G. S., Merke, D. P., Meyer-Bahlburg, H. F. L., Miller, W. L., Murad, M. H., Oberfield, S. E., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01865 · Cited by 1,234 · see citing works
Krueger, C., & Tian, L. (2004) · Biological Research For Nursing · doi:10.1177/1099800404267682 · Cited by 561 · see citing works
The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids
Oster, H., Challet, E., Ott, V., Arvat, E., de Kloet, E. R., Dijk, D.-J., Lightman, S., Vgontzas, A., & Van Cauter, E. (2017) · Endocrine Reviews · doi:10.1210/er.2015-1080 · Cited by 548 · see citing works
Son, G. H., Chung, S., Choe, H. K., Kim, H.-D., Baik, S. M., Lee, H., Lee, H., Choi, S., Sun, W., Kim, H., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806962106 · Cited by 316 · see citing works
Circadian rhythm of adrenal glucocorticoid: its regulation and clinical implications
Chung, S., Son, G. H., & Kim, K. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.02.003 · Cited by 305 · see citing works
Speiser, P., Arlt, W., Rj, A., Baskin, L., Conway, G. S., Merke, D. P., Meyer‐Bahlburg, H. F. L., Miller, W. L., Murad, M. H., Oberfield, S., et al. (2019) · Yearbook of pediatric endocrinology · doi:10.1530/ey.16.8.5 · Cited by 301 · see citing works
Spiga, F., Walker, J. J., Terry, J. R., & Lightman, S. L. (2014) · Comprehensive Physiology · doi:10.1002/cphy.c140003 · Cited by 267 · see citing works
11-Oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome
O’Reilly, M. W., Kempegowda, P., Jenkinson, C., Taylor, A. E., Quanson, J. L., Storbeck, K.-H., & Arlt, W. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3285 · Cited by 267 · see citing works
Turcu, A. F., Nanba, A. T., Chomic, R., Upadhyay, S. K., Giordano, T. J., Shields, J. J., Merke, D. P., Rainey, W. E., & Auchus, R. J. (2016) · European Journal of Endocrinology · doi:10.1530/eje-15-1181 · Cited by 231 · see citing works
Newborn screening for congenital adrenal hyperplasia
Therrell, B. L. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(08)70017-3 · Cited by 221 · see citing works
11-Oxygenated androgens in health and disease
Turcu, A. F., Rege, J., Auchus, R. J., & Rainey, W. E. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0336-x · Cited by 217 · see citing works
Kamrath, C., Hochberg, Z., Hartmann, M. F., Remer, T., & Wudy, S. A. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1997 · Cited by 191 · see citing works
Adrenal Steroidogenesis and Congenital Adrenal Hyperplasia
Turcu, A. F., & Auchus, R. J. (2015) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.02.002 · Cited by 177 · see citing works
A new dawn for androgens: novel lessons from 11-oxygenated C19 steroids
Pretorius, E., Arlt, W., & Storbeck, K.-H. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.08.014 · Cited by 142 · see citing works
Steroid Metabolome Analysis in Disorders of Adrenal Steroid Biosynthesis and Metabolism
Storbeck, K.-H., Schiffer, L., Baranowski, E. S., Chortis, V., Prete, A., Barnard, L., Gilligan, L. C., Taylor, A. E., Idkowiak, J., Arlt, W., et al. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00262 · Cited by 141 · see citing works
Deterding, K., Spinner, C. D., Schott, E., Welzel, T. M., Gerken, G., Klinker, H., Spengler, U., Wiegand, J., Wiesch, J. S. Z., Pathil, A., et al. (2016) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(16)30408-x · Cited by 129 · see citing works
Approach to the patient: the adult with congenital adrenal hyperplasia
Auchus, R. J., & Arlt, W. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-1440 · Cited by 121 · see citing works
Turcu, A. F., Mallappa, A., Elman, M. S., Avila, N. A., Marko, J., Rao, H., Tsodikov, A., Auchus, R. J., & Merke, D. P. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-3989 · Cited by 107 · see citing works
Impact of ACTH Signaling on Transcriptional Regulation of Steroidogenic Genes
Ruggiero, C., & Lalli, E. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00024 · Cited by 95 · see citing works
Quanson, J. L., Stander, M. A., Pretorius, E., Jenkinson, C., TAYLOR, A. E. R., & Storbeck, K. (2016) · Journal of Chromatography B · doi:10.1016/j.jchromb.2016.07.024 · Cited by 74 · see citing works
Monitoring of Therapy in Congenital Adrenal Hyperplasia
Dauber, A. N., Kellogg, M. D., & Majzoub, J. A. (2010) · Clinical Chemistry · doi:10.1373/clinchem.2010.146035 · Cited by 72 · see citing works
Kamrath, C., Wettstaedt, L., Boettcher, C., Hartmann, M. F., & Wudy, S. A. (2018) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.12.016 · Cited by 71 · see citing works
Management considerations for the adult with congenital adrenal hyperplasia
Auchus, R. J. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.039 · Cited by 65 · see citing works
Persisting Muscle Dysfunction in Cushing’s Syndrome Despite Biochemical Remission
Vogel, F., Braun, L., Rubinstein, G., Zopp, S., Kunzel, H. E., Strasding, F., Albani, A., Riester, A., Schmidmaier, R., Bidlingmaier, M., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa625 · Cited by 62 · see citing works
Self-citationDebono, M., Mallappa, A., Gounden, V., Nella, A. A., Harrison, R. F., Crutchfield, C. A., Backlund, P. S., Soldin, S. J., Ross, R. J., & Merke, D. P. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0064 · Cited by 53 · see citing works
Advances in the analytical methodologies: profiling steroids in familiar pathways-challenging dogmas
Bloem, L. M., Storbeck, K.-H., Swart, P., du Toit, T., Schloms, L., & Swart, A. C. (2015) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.04.009 · Cited by 52 · see citing works
Bode, H. H., Rivkees, S. A., Cowley, D. M., Pardy, K., & Johnson, S. (1999) · The Journal of Pediatrics · doi:10.1016/s0022-3476(99)70413-0 · Cited by 47 · see citing works
Bacila, I. A., Adaway, J., Hawley, J. M., Mahdi, S., Krone, R. E., Patel, L., Alvi, S., Randell, T. L., Gevers, E. F., Dattani, M., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00031 · Cited by 44 · see citing works
Self-citationSHIBAYAMA, Y., Higashi, T., Shimada, K., Kashimada, K., ONISHI, T., Ono, M., Miyai, K., & MIZUTANI, S. (2008) · Journal of Chromatography B · doi:10.1016/j.jchromb.2008.03.009 · Cited by 43 · see citing works
Mezzullo, M., Fazzini, A., Gambineri, A., Dalmazi, G. D., Mazza, R., Pelusi, C., Vicennati, V., Pasquali, R., Pagotto, U., & Fanelli, F. (2017) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0805 · Cited by 39 · see citing works
Ali, S. R., Bryce, J., Haghpanahan, H., Lewsey, J. D., Tan, L. E., Atapattu, N., Birkebaek, N. H., Blankenstein, O., Neumann, U., Balsamo, A., et al. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa694 · Cited by 39 · see citing works
Dahl, S. R., Nermoen, I., Brønstad, I., Husebye, E. S., Løvås, K., & Thorsby, P. M. (2018) · Endocrine Connections · doi:10.1530/ec-18-0453 · Cited by 28 · see citing works
Lee, P. A., Urban, M. D., Gutai, J. P., & Migeon, C. J. (2008) · Hormone Research · doi:10.1159/000179303 · Cited by 27 · see citing works
Androgens in Congenital Adrenal Hyperplasia
Pignatelli, D., Pereira, S. S., & Pasquali, R. (2019) · Frontiers of hormone research · doi:10.1159/000494903 · Cited by 26 · see citing works
Schiffer, L., Adaway, J., Arlt, W., & Keevil, B. G. (2019) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/0004563219847498 · Cited by 20 · see citing works
Self-citationde Groot, M. J. M., Pijnenburg-Kleizen, K. J., Thomas, C. M. G., Sweep, F. C. G. J., Stikkelbroeck, N. M. M. L., Otten, B. J., & Claahsen-van der Grinten, H. L. (2015) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2014-0375 · Cited by 18 · see citing works
Juniarto, A. Z., Goossens, K., Setyawati, B. A., Drop, S. L. S., de Jong, F. H., & Faradz, S. M. (2011) · PubMed · Cited by 16 · see citing works
Jha, S., El‐Maouche, D., Marko, J., Mallappa, A., Veeraraghavan, P., & Merke, D. P. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00227 · Cited by 16 · see citing works
Auer, M. K., Krumbholz, A., Bidlingmaier, M., Thieme, D., & Reisch, N. (2019) · Neuroendocrinology · doi:10.1159/000504672 · Cited by 13 · see citing works
Self-citation
Flagged first, then by citations
1 of the 41 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Congenital adrenal hyperplasia
Auer, M. K., Nordenström, A., Lajić, S., & Reisch, N. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01330-7 · Cited by 232 · see citing works
Self-citationThe clinical and biochemical significance of 11-oxygenated androgens in human health and disease
Storbeck, K.-H., & O’Reilly, M. W. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad047 · Cited by 63 · see citing works
Schiffer, L., Kempegowda, P., Sitch, A. J., Adaway, J. E., Shaheen, F., Ebbehoj, A., Singh, S., McTaggart, M. P., O’Reilly, M. W., Prete, A., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvac017 · Cited by 42 · see citing works
Self-citationNovel treatments for congenital adrenal hyperplasia
Schröder, M. A. M., & der Grinten, H. L. C. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09717-w · Cited by 29 · see citing works
Nowotny, H. F., Braun, L., Vogel, F., Bidlingmaier, M., Reincke, M., Tschaidse, L., Auer, M. K., Lottspeich, C., Wudy, S. A., Hartmann, M. F., et al. (2022) · European Journal of Endocrinology · doi:10.1530/eje-22-0320 · Cited by 28 · see citing works
Self-citationTurcu, A. F., Mallappa, A., Nella, A. A., Chen, X., Zhao, L., Nanba, A. T., Byrd, J. B., Auchus, R. J., & Merke, D. P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.751191 · Cited by 20 · see citing works
Biomarkers in congenital adrenal hyperplasia
Bacila, I. A., Lawrence, N., Badrinath, S. G., Balagamage, C., & Krone, N. P. (2023) · Clinical Endocrinology · doi:10.1111/cen.14960 · Cited by 23 · see citing works
Sarafoglou, K., & Auchus, R. J. (2024) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae759 · Cited by 16 · see citing works
Saco, Y., Peña, R., Matas-Quintanilla, M., Ibáñez‐López, F. J., Piñeiro, M., Sotillo, J., Bassols, A., & Gutiérrez, A. M. (2023) · Porcine Health Management · doi:10.1186/s40813-023-00337-7 · Cited by 8 · see citing works
Nowotny, H. F., Seiter, T. M., Ju, J., Gottschlich, A., Schneider, H., Zopp, S., Vogel, F., Tschaidse, L., Auer, M. K., Lottspeich, C., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1275828 · Cited by 7 · see citing works
Self-citationDahl, S. R., Bakke, L. H., Thorsby, P. M., & Zykova, S. N. (2024) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2024.2437620 · Cited by 6 · see citing works
Kamrath, C., Friedrich, C., Hartmann, M. F., & Wudy, S. A. (2023) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2023.106304 · Cited by 7 · see citing works
The Landscape of Androgens in Cushing’s Syndrome
Nowotny, H. F., Braun, L., & Reisch, N. (2024) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2333-1907 · Cited by 5 · see citing works
Self-citationDubinski, I., Bechtold, S. M., Bidlingmaier, M., Reisch, N., & Schmidt, H. (2022) · Hormone Research in Paediatrics · doi:10.1159/000526485 · Cited by 7 · see citing works
Self-citationDubinski, I., Pozza, S. B., Bidlingmaier, M., Hawley, J. M., Keevil, B. G., Kunz, S. L., Nowotny, H. F., Reisch, N., Schiergens, K. A., Tschaidse, L., et al. (2024) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2024-0027 · Cited by 2 · see citing works
Self-citationDiurnal variation in salivary testosterone independent of food consumption
Fenn, J. S., Gill, H., Kalaria, T., Starbrook, L., Ford, L. T., Sharrod–Cole, H., Ford, C., & Gama, R. M. (2025) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/00045632251357140 · Cited by 1 · see citing works
Current insights into monitoring of congenital adrenal hyperplasia
Leusink, Q. M., Verploegen, E., Adriaansen, B. P. H., Chin, X., Stikkelbroeck, N. M. M. L., Span, P. N., Sweep, F. C. G. J., Dona, M., van Herwaarden, A. E., & der Grinten, H. L. C. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1774145 · Cited by 1 · see citing works
Park, J., Titman, A., Bright, O., Dliso, S., Shantsila, A., Lip, G. Y. H., Adaway, J., Keevil, B. G., Hawcutt, D. B., & Blair, J. (2025) · Clinical Endocrinology · doi:10.1111/cen.15258 · Cited by 1 · see citing works
Self-citationАнатольевич, Т. М., Kalinchenko, N. Y., Быченков, Д. В., Иоутси, В. А., Antsupova, M. A., Elfimova, A. R., & Nagaeva, E. V. (2025) · Problems of Endocrinology · doi:10.14341/probl13551
Saco, Y., Peña, R., Matas-Quintanilla, M., Ibáñez-López, F. J., Piñeiro, M., Sotillo, J., Bassols, A., & Gutiérrez, A. M. (2024) · Figshare · doi:10.6084/m9.figshare.26620933
Jin, X., Werner, H. M. J., & Romano, A. (2026) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2026.106958
Real-world outcomes with modified-release hydrocortisone in classic congenital adrenal hyperplasia
Auer, M. K., Bayer, K., Nowotny, H. F., Tschaidse, L., Dervishi, O., Welp, A.-C., Lottspeich, C., Bidlingmaier, M., Kunz, S. L., & Reisch, N. (2026) · European Journal of Endocrinology · doi:10.1093/ejendo/lvag087
Self-citation
- Authors
- Nowotny, H. F., Auer, M. K., Lottspeich, C., Schmidt, H., Dubinski, I., Bidlingmaier, M., Adaway, J., Hawley, J., Keevil, B., & Reisch, N.
- Affiliations
- LMU Klinikum (DE)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Reisch, Nicole
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2021-06-24
- Volume
- 106
- Issue
- 11
- Pages
- e4509-e4519
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC8530726
- OpenAlex
- W3173599338
- Cited by
- 22
- References
- 41
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 1
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by-nc-nd)
- medRxiv (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc-nd)
- Funders
- Deutsche Forschungsgemeinschaft (325768017, 314061271-TRR205)
- Eva Luise und Horst Köhler Stiftung & Else Kröner-Fresenius-Stiftung (2019_KollegSE.03)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- congenital adrenal hyperplasia, 21-hydroxylase deficiency, 11-oxygenated androgens, diurnal cycle, salivary steroids, 17-hydroxyprogesterone, 11-ketotestosterone, 11β-hydroxyandrostenedione, androstenedione, disease surveillance
- MeSH terms
- Adrenal Hyperplasia, Congenital, Adult, Androgens, Androstenedione, Circadian Rhythm, Cross-Sectional Studies, Female, Humans, Male, Saliva, Testosterone, Biomarkers, 17-alpha-Hydroxyprogesterone
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
