Long-term follow-up of a female with congenital adrenal hyperplasia due to P450-oxidoreductase deficiency
Open accessAbstract
P450 oxidoreductase deficiency (PORD) is a variant of congenital adrenal hyperplasia that is caused by POR gene mutations. The POR gene encodes a flavor protein that transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to all microsomal cytochrome P450 type II (including 21-hydroxylase, 17α-hydroxylase 17,20 lyase and aromatase), which is fundamental for their enzymatic activity. POR mutations cause variable impairments in steroidogenic enzyme activities that result in wide phenotypic variability ranging from 46,XX or 46,XY disorders of sexual differentiation, glucocorticoid deficiency, with or without skeletal malformations similar to Antley-Bixler syndrome to asymptomatic newborns diagnosed during neonatal screening test. Little is known about the PORD long-term evolution. We described a 46,XX patient with mild atypical genitalia associated with severe bone malformation, who was diagnosed after 13 years due to sexual infantilism. She developed large ovarian cysts and late onset adrenal insufficiency during follow-up, both of each regressed after hormone replacement therapies. We also described a late surgical approach for the correction of facial hypoplasia in a POR patient.
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?
Approximately half of all PORD patients require lifelong hydrocortisone replacement, while others may only need supplemental doses during periods of physiologic stress.
“While approximately half of all PORD patients require lifelong hydrocortisone replacement, others may only need supplemental doses during periods of physiologic stress (21, 28, 34).”
From Case Report: Integrating clinical presentation and genetic analysis in P450 oxidoreductase deficiency: a novel mutation and systematic review (2026) · cites this paper as [28]
The Discussion reports that 50% of PORD patients in large cohorts needed permanent hydrocortisone. The Case Report describes stress-dose glucocorticoids during surgery, but its patient later needed ongoing therapy; it does not establish that other patients need supplementation only during physiologic stress. No page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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
Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome
Flück, C. E., Tajima, T., Pandey, A. V., Arlt, W., Okuhara, K., Verge, C. F., Jabs, E. W., Mendonça, B. B., Fujieda, K., & Miller, W. L. (2004) · Nature Genetics · doi:10.1038/ng1300 · Cited by 509 · cited 4× · see citing works
“Notably, high blood pressure due to increased DOCA and impairment of 17α-hydroxylase was reported (1).”
BackgroundInfluentialSelf-citationChemical structure of sterols that activate oocyte meiosis
Byskov, A. G., Andersen, C. Y., Nordholm, L., Thøgersen, H., Guoliang, X., Wassmann, O., Andersen, J. V., Guddal, E., & Roed, T. (1995) · Nature · doi:10.1038/374559a0 · Cited by 354 · see citing works
Latronico, A. C., Anasti, J. N., Arnhold, I. J. P., Rapaport, R., Mendonca, B. B., BLOISE, W., de Castro, M., Tsigos, C., & Chrousos, G. P. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602223340805 · Cited by 351 · see citing works
Self-citationArlt, W., Walker, E. A., Draper, N., Ivison, H. E., Ride, J. P., Hammer, F., Chalder, S. M., Borucka-Mankiewicz, M., Hauffa, B. P., Malunowicz, E. M., et al. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16503-3 · Cited by 345 · see citing works
Huang, N., Pandey, A. V., Agrawal, V., Reardon, W., Lapunzina, P. D., Mowat, D., Jabs, E. W., Vliet, G. V., Sack, J., Flück, C. E., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/429417 · Cited by 336 · see citing works
Minireview: Regulation of Steroidogenesis by Electron Transfer
Miller, W. L. (2005) · Endocrinology · doi:10.1210/en.2005-0096 · Cited by 324 · see citing works
Mathijssen, I. M. J. (2015) · Journal of Craniofacial Surgery · doi:10.1097/scs.0000000000002016 · Cited by 232 · see citing works
Latronico, A. C., Anasti, J. N., Arnhold, I. J. P., Rapaport, R., Mendonca, B. B., BLOISE, W., de Castro, M., Tsigos, C., & Chrousos, G. P. (1996) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-199607000-00017 · Cited by 167 · see citing works
Self-citationGenotype-Phenotype Analysis in Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency
Krone, N., Reisch, N., Idkowiak, J., Dhir, V., Ivison, H. E., Hughes, B. A., Rose, I. T., O'Neil, D. M., Vijzelaar, R., Smith, M. J., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0640 · Cited by 163 · cited 5× · see citing works
“A287P mutation in homozygosis, which is the most frequent mutation in Caucasians, and it is observed in approximately 43% of nonrelated alleles (8).”
BackgroundInfluentialFukami, M., Nishimura, G., Homma, K., Nagai, T., Hanaki, K., Uematsu, A., Ishii, T., Numakura, C., Sawada, H., Nakacho, M., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2816 · Cited by 117 · see citing works
Genetic and clinical features of P450 oxidoreductase deficiency
Scott, R. R., & Miller, W. L. (2008) · Hormone Research in Paediatrics · doi:10.1159/000114857 · Cited by 115 · see citing works
Hershkovitz, E., Parvari, R., Wudy, S. A., Hartmann, M. F., Gomes, L. G., Loewental, N., & Miller, W. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0051 · Cited by 95 · see citing works
Self-citationDifferential Inhibition of CYP17A1 and CYP21A2 Activities by the P450 Oxidoreductase Mutant A287P
Dhir, V., Ivison, H. E., Krone, N., Shackleton, C. H. L., Doherty, A. J., Stewart, P. M., & Arlt, W. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0066 · Cited by 78 · see citing works
Of marsupials and men: “Backdoor” dihydrotestosterone synthesis in male sexual differentiation
Biason-Lauber, A., Miller, W. L., Pandey, A. V., & Flück, C. E. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.01.017 · Cited by 69 · see citing works
Prenatal diagnosis of congenital adrenal hyperplasia caused by P450 oxidoreductase deficiency
Reisch, N., Idkowiak, J., Hughes, B. A., Ivison, H. E., Abdul-Rahman, O. A., Hendon, L. G., Olney, A. H., Nielsen, S., Harrison, R., Blair, E. M., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3449 · Cited by 67 · see citing works
Idkowiak, J., O'Riordan, S., Reisch, N., Malunowicz, E. M., Collins, F., Kerstens, M. N., Köhler, B., Graul-Neumann, L. M., Szarras-Czapnik, M., Dattani, M., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1607 · Cited by 64 · see citing works
Clinical and Biochemical Consequences of P450 Oxidoreductase Deficiency
Flück, C. E., & Pandey, A. V. (2010) · Endocrine development · doi:10.1159/000321221 · Cited by 50 · see citing works
Human oocyte maturation in vitro is stimulated by meiosis-activating sterol
Grøndahl, C., Hansen, T. H., Marky-Nielsen, K., Ottesen, J. L., & Hyttel, P. (2000) · Human Reproduction · doi:10.1093/humrep/15.suppl_5.3 · Cited by 43 · see citing works
Spectrum of Antley-Bixler Syndrome
McGlaughlin, K., Witherow, H., Dunaway, D. J., David, D. J., & Anderson, P. J. (2010) · Journal of Craniofacial Surgery · doi:10.1097/scs.0b013e3181ec6afe · Cited by 41 · see citing works
de Carvalho, L. C., Brito, V. N., Martin, R. M., Zamboni, A. M., Gomes, L. G., Inácio, M., Mermejo, L. M., Coeli‐Lacchini, F. B., Teixeira, V. R., Gonçalves, F. T., et al. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.02.008 · Cited by 33 · see citing works
Self-citationGuaragna‐Filho, G., Castro, C. C. T. D. S., Carvalho, R. R. D., Coeli, F. B., Ferraz, L. F. C., Petroli, R. J., de Mello, M. P., SEWAYBRICKER, L. E., de Lemos‐Marini, S. H. V., D’Souza-Li, L. F. R., et al. (2012) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302012000800020 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Classic congenital adrenal hyperplasia and its impact on reproduction
Gomes, L. G., Bachega, T. A. S. S., & Mendonca, B. B. (2019) · Fertility and Sterility · doi:10.1016/j.fertnstert.2018.11.037 · Cited by 58 · see citing works
Self-citationDean, B., Chrisp, G. L., Quartararo, M., Maguire, A. M., Hameed, S., King, B. R., Munns, C. F., Torpy, D. J., Falhammar, H., & Rushworth, R. L. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz255 · Cited by 43 · see citing works
Witchel, S. F., & Topaloglu, A. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-323-47912-7.00017-2 · Cited by 40 · see citing works
Bai, Y., Li, J., & Wang, X. (2017) · Journal of Ovarian Research · doi:10.1186/s13048-017-0312-9 · Cited by 34 · see citing works
Therapeutic liver repopulation by transient acetaminophen selection of gene-modified hepatocytes
Vonada, A., Tiyaboonchai, A., Nygaard, S. C., Posey, J., Peters, A. M., Winn, S. R., Cantore, A., Naldini, L., Harding, C. O., & Grompe, M. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abg3047 · Cited by 33 · see citing works
Congenital Adrenal Hyperplasias Presenting in the Newborn and Young Infant
Balsamo, A., Baronio, F., Ortolano, R., Menabò, S., Baldazzi, L., Natale, V. D., Vissani, S., & Cassio, A. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.593315 · Cited by 26 · see citing works
Parween, S., Velazquez, M. N. R., Udhane, S. S., Kagawa, N., & Pandey, A. V. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01187 · Cited by 24 · see citing works
Gusmano, C., Cannarella, R., Crafa, A., Barbagallo, F., Vignera, S. L., Condorelli, R. A., & Calogero, A. E. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01849-9 · Cited by 16 · see citing works
Acharya, K. S., Schrott, R., Grenier, C., Huang, Z., Holloway, Z., Hawkey, A. B., Levin, E. D., & Murphy, S. K. (2020) · Scientific Reports · doi:10.1038/s41598-020-69204-7 · Cited by 12 · see citing works
Wang, C., & Tian, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1226387 · Cited by 11 · see citing works
Clinical characteristics of cytochrome P450 oxidoreductase deficiency: a nationwide survey in Japan
Yatsuga, S., Amano, N., Nakamura-Utsunomiya, A., Kobayashi, H., Takasawa, K., Nagasaki, K., Nakamura, A., Nishigaki, S., Numakura, C., Fujiwara, I., et al. (2020) · Endocrine Journal · doi:10.1507/endocrj.ej20-0011 · Cited by 9 · see citing works
In Silico Analysis of PORD Mutations on the 3D Structure of P450 Oxidoreductase
Nurhafizuddin, M., Azizi, A., Ming, L. C., & Shafqat, N. (2022) · Molecules · doi:10.3390/molecules27144646 · Cited by 7 · see citing works
P450 oxidoreductase deficiency
Flück, C. E., Velazquez, M. N. R., & Pandey, A. V. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-821424-4.00012-5 · Cited by 3 · see citing works
Gluvic, Z. M., Samardzic, V. S., Zarić, B. L., Đurković, V., Mladenović, V., Stojanović, M., & Isenović, E. R. (2017) · Medicinska istrazivanja · doi:10.5937/medist1703029g · Cited by 1 · see citing works
Shafqat, N., Amdani, S. N., & Ming, L. C. (2024) · Journal of Research in Pharmacy · doi:10.29228/jrp.718
Zhang, C., Zhao, Z., Du, Y., Huang, Q., Liu, Y., Fu, G., & Xu, J. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1791297
Dean, B. W., Chrisp, G. L., Quartararo, M., Maguire, A. M., Hameed, S. S., Br, K., Munns, C. F., Torpy, D. J., Falhammar, H., & Rushworth, R. L. (2020) · Yearbook of pediatric endocrinology · doi:10.1530/ey.17.8.21 · Cited by 1 · see citing works
Human P450 oxidoreductase deficiency
Pandey, A. V., Barata, I. S., & Flück, C. E. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00259-4
A Two-Step LC-MS/MS method to differentiate 21OHD and PORD in Screen-Positive newborns
Nakatani, H., Watanabe, K., Tsuji‐Hosokawa, A., Sutani, A., Saito, Y., Kirino, S., Yamano, H., Orimoto, R., Gau, M., Yogi, A., et al. (2026) · Endocrine · doi:10.1007/s12020-026-04573-z
- Authors
- Bonamichi, B. D. S. F., Santiago, S. L. M., Bertola, D. R., Kim, C. A., Alonso, N., Mendonca, B. B., Bachega, T. A. S. S., & Gomes, L. G.
- Affiliations
- Irmandade da Santa Casa de Misericórdia de São Paulo (BR)
- Universidade de São Paulo (BR)
- Faculdade de Medicina da Universidade de São Paulo, Brasil
- Venue
- Archives of Endocrinology and Metabolism
- Published
- 2016-10
- Volume
- 60
- Issue
- 5
- Pages
- 500-504
- ISSN
- 2359-3997 (ISSN-L)
- PMC
- PMC10118638
- OpenAlex
- W2528099780
- Cited by
- 19
- References
- 21
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 4 · 2017: 2
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Archives of Endocrinology and Metabolism (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (308318/2012-9)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- P450 oxidoreductase deficiency, congenital adrenal hyperplasia, long-term follow-up, 46,XX disorders of sex development, ambiguous genitalia, bone malformations, Antley-Bixler syndrome, adrenal insufficiency, ovarian cysts, hormone replacement therapy, facial hypoplasia, steroidogenesis
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
