Mitotane for 21-hydroxylase deficiency in an infertile man
Open accessAbstract
To the Editor: In our original report, 1 we used a method based on polymerase-chain-reaction (PCR) amplification developed in our laboratory to perform KIR genotyping. 2 We have retyped 1220 of the original 1277 donor samples using three separate published or commercial genetyping methods (PCR-sequence-specific primers [SSP] and PCR-sequence-specific oligonucleotide probe [SSOP]), and we have repeated the analysis on the retyped cohort.For KIR2DS1, typing was confirmed in 1146 (94%) of the 1220 retested samples and corrected in 74 (6%) of the retested samples.For KIR3DS1, typing was confirmed in 1133 (93%) and corrected in 83 (7%).Differences in typing results came from two sources: from errors made in the performance of the original PCR-SSP-based typing and from a recombinant allele that typed as the activating KIR3DS1 in the original PCR-SSP typing but types as an inhibitory KIR3DL1 allele when contemporary typing methods (PCR-SSP and PCR-SSOP) are used.Gene frequencies in the original and retyped cohorts were nearly identical (KIR2DS1, 33% positive in the original cohort and 34% positive in the retyped cohort; KIR3DS1, 34% positive in the original cohort and 33% positive in the retyped cohort).Analysis of the clinical effect of KIR2DS1 and HLA-C in the retyped cohort revealed results that were similar to those from the original analysis.We have provided figures and associations from the original analysis of 1277 patients in juxtaposition with figures and associations from the retyped cohort of 1220 in the Supplementary Appendix, available with the full text of this letter at NEJM.org.Our conclusions regarding the protective effect of donor KIR2DS1 on relapse and the influence of donor and recipient HLA-C on this effect are unchanged.These and other conclusions are summarized in the Supplementary Appendix.
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?
Mitotane was successfully used to shrink TART and restore fertility in a 29-year-old male with classic 21OH deficiency.
“Mitotane was successfully used to shrink TART and restore fertility in a 29-year-old male with classic 21OH deficiency.147”
From Congenital adrenal hyperplasia (2017) · cites this paper as [147]
Successful restoration of fertility was first achieved with mitotane therapy in a 29-year-old man with classic CAH and bilateral TARTs associated with hypogonadism and azoospermia.
“Successful restoration of fertility was first achieved with mitotane therapy in a 29-year-old man with classic CAH and bilateral TARTs associated with hypogonadism and azoospermia152.”
From Management challenges and therapeutic advances in congenital adrenal hyperplasia (2022) · cites this paper as [152]
Mitotane is rarely used off-label in management of Cushing disease and in CAH in the context of infertility due to TART.
“Mitotane is also rarely used (off-label) in the management of Cushing disease151 and in CAH in the context of infertility due to TART152,153.”
From Management challenges and therapeutic advances in congenital adrenal hyperplasia (2022) · cites this paper as [152]
In that same case, sperm count ultimately increased and paternity was achieved.
“Ultimately, sperm count increased, and paternity was achieved.”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [326]
In a man with classic CAH and testicular adrenal rest tumors who had been infertile for 2 years, mitotane reduced adrenal-derived androgen precursors and caused TART regression despite a rise in ACTH.
“Adrenalderived androgen precursors declined, and TARTs regressed, despite a rise in ACTH.”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [326]
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
Kamenický, P., Droumaguet, C., Salenave, S., Blanchard, A., Jublanc, C., Gautier, J., Brailly‐Tabard, S., Leboulleux, S., Schlumberger, M. J., Baudin, É., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0536 · Cited by 218 · see citing works
Self-citationTesticular adrenal rest tumours in congenital adrenal hyperplasia
Claahsen-van der Grinten, H. L., Otten, B. J., Stikkelbroeck, M. M. L., Sweep, F. C. G. J., & Hermus, A. R. M. M. (2009) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2008.09.007 · Cited by 187 · see citing works
Chortis, V., Taylor, A. E., Schneider, P., Tomlinson, J. W., Hughes, B. A., O'Neil, D. M., Libé, R., Allolio, B., Bertagna, X., Bertherat, J., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2851 · Cited by 154 · see citing works
Hescot, S., Slama, A., Lombès, A., Paci, A., Remy, H., Leboulleux, S., Chadarévian, R., Trabado, S., Amazit, L., Young, J., et al. (2013) · Endocrine Related Cancer · doi:10.1530/erc-12-0368 · Cited by 98 · see citing works
Self-citationGmyrek, G. A., New, M. I., Sosa, R. E., & Poppas, D. P. (2002) · PEDIATRICS · doi:10.1542/peds.109.2.e28 · Cited by 41 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Congenital adrenal hyperplasia
El-Maouche, D., Arlt, W., & Merke, D. P. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31431-9 · Cited by 669 · see citing works
Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
Claahsen - van der Grinten, H. L., Speiser, P. W., Ahmed, S. F., Arlt, W., Auchus, R. J., Falhammar, H., Flück, C. E., Guasti, L., Huebner, A., Kortmann, B. B. M., et al. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab016 · Cited by 556 · see citing works
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Merke, D. P., & Auchus, R. J. (2020) · New England Journal of Medicine · doi:10.1056/nejmra1909786 · Cited by 341 · see citing works
Engels, M., Span, P. N., van Herwaarden, A. E., Sweep, F. C. G. J., Stikkelbroeck, N. M. M. L., & Claahsen-van der Grinten, H. L. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00258 · Cited by 163 · see citing works
Bouvattier, C., Esterle, L., Renoult-Pierre, P., de la Perrière, A. B., Illouz, F., Kerlan, V., Pascal-Vigneron, V., Drui, D., Christin-Maitre, S., Galland, F., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4124 · Cited by 116 · see citing works
Self-citationManagement challenges and therapeutic advances in congenital adrenal hyperplasia
Mallappa, A., & Merke, D. P. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00655-w · Cited by 113 · see citing works
MANAGEMENT OF ENDOCRINE DISEASE: Gonadal dysfunction in congenital adrenal hyperplasia
Claahsen-van der Grinten, H. L., Stikkelbroeck, N., Falhammar, H., & Reisch, N. (2021) · European Journal of Endocrinology · doi:10.1530/eje-20-1093 · Cited by 72 · see citing works
Bachelot, A., Lapoirie, M., Dulon, J., Leban, M., Renard Penna, R., & Touraine, P. (2021) · European Journal of Endocrinology · doi:10.1530/eje-20-0787 · Cited by 19 · see citing works
Kavoussi, P. K., Summers-Colquitt, R. B., Odenwald, K. C., Kressin, M., Kavoussi, K. M., Pool, T. B., & Kavoussi, S. K. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0665-9 · Cited by 17 · see citing works
- Authors
- Bry-Gauillard, H., Cartes, A., & Young, J.
- ORCID
- Young, Jacques
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2014-11-20
- Volume
- 371
- Issue
- 21
- Pages
- 2042-2044
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2319603627
- Cited by
- 38
- References
- 5
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 2
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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
- mitotane, 21-hydroxylase deficiency, congenital adrenal hyperplasia, male infertility, KIR genotyping, KIR2DS1, KIR3DS1, KIR3DL1, HLA-C
- MeSH terms
- Adrenal Hyperplasia, Congenital, Adrenal Rest Tumor, Adult, Gonadotropins, Hormones, Humans, Male, Mitotane, Mutation, Steroid 21-Hydroxylase, Testicular Neoplasms, Testis, Antineoplastic Agents, Hormonal, Azoospermia
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
