{ "schemaVersion": 2, "eyebrow": "Endocrinology", "title": "21-Hydroxylase Deficiency", "summary": "Diagnose suspected 21-hydroxylase deficiency with properly timed 17-hydroxyprogesterone testing, urgently identify salt-wasting risk in newborns, and use cosyntropin steroid profiling and genotyping to resolve equivocal cases while guiding endocrine management and family counseling.", "seoDescription": "Physician guide to diagnosing 21-hydroxylase deficiency, assessing neonatal salt-wasting risk, and using 17-hydroxyprogesterone and cosyntropin testing.", "clinicalQuestion": "How should clinicians confirm 21-hydroxylase deficiency and identify patients at risk for salt-wasting adrenal crisis?", "specialty": "Endocrinology", "audience": "U.S. physicians and medical trainees", "tags": [ "21-hydroxylase deficiency", "CYP21A2", "congenital adrenal hyperplasia", "17-hydroxyprogesterone", "cosyntropin stimulation", "salt-wasting crisis" ], "keyTakeaways": [ "21-Hydroxylase deficiency accounts for more than 90% of congenital adrenal hyperplasia and is the most common genetic cause of primary adrenal insufficiency. [4][15][8]", "A positive newborn screen requires pediatric endocrine assessment, confirmatory serum 17-hydroxyprogesterone measurement, and electrolyte plus plasma renin assessment for salt-wasting risk. [22][23]", "In symptomatic patients beyond infancy, obtain an early-morning, pre-8 AM serum 17-hydroxyprogesterone by LC-MS/MS; collect during the early follicular phase in menstruating patients. [22]", "Use cosyntropin stimulation with a complete adrenal steroid profile when baseline 17-hydroxyprogesterone is borderline or biochemical results do not distinguish 21-hydroxylase deficiency from another steroidogenic defect. [22][24]", "Classic disease can cause cortisol and aldosterone deficiency with life-threatening neonatal salt-wasting crisis; hyperkalemia, electrolyte abnormalities, and elevated plasma renin identify mineralocorticoid compromise. [8][23]" ], "sections": [ { "id": "triage-and-clinical-branching", "eyebrow": "Immediate decisions", "heading": "Identify salt-wasting risk before completing etiologic confirmation", "intro": "Treat newborn evaluation as an adrenal-insufficiency risk assessment, not merely an abnormal screening result.", "paragraphs": [ "In a newborn with a screen suggestive of 21-hydroxylase deficiency, arrange urgent pediatric endocrinology assessment and obtain confirmatory serum 17-hydroxyprogesterone, serum electrolytes, and plasma renin activity. Electrolyte disturbance and renin elevation identify infants at risk for salt-wasting crisis. [22][23]", "Classic 21-hydroxylase deficiency reduces cortisol synthesis and can reduce aldosterone synthesis; affected infants may develop life-threatening salt-wasting crisis. Female fetuses with classic disease may have virilization from androgen excess, but absence of ambiguous genitalia does not reduce concern for adrenal insufficiency in an infant with an abnormal screen. [8][24]", "If clinical concern for classic congenital adrenal hyperplasia is high, cosyntropin testing can be performed at 48 to 72 hours of life, and glucocorticoid treatment is often started while confirmatory results are pending. [24]" ], "bullets": [ "Obtain serum electrolytes and plasma renin activity at initial neonatal assessment to define mineralocorticoid risk. [23]", "Refer infants with positive newborn screening results to pediatric endocrinology; use cosyntropin testing when confirmation is needed. [22]", "Do not wait for a random later 17-hydroxyprogesterone level when salt-wasting disease is clinically plausible; early treatment may be initiated during diagnostic evaluation. [24]" ], "subsections": [], "table": { "caption": "Clinical branches after an abnormal newborn screen for congenital adrenal hyperplasia. [22][23][24]", "columns": [ "Finding", "Interpretation", "Next action" ], "rows": [ [ "Elevated serum 17-hydroxyprogesterone after positive screen", "Supports 21-hydroxylase deficiency; confirm biochemical phenotype. [23]", "Assess electrolytes and plasma renin activity; involve pediatric endocrinology. [22][23]" ], [ "Electrolyte abnormalities and/or elevated plasma renin activity", "Identifies risk for salt-wasting crisis from mineralocorticoid deficiency. [23]", "Manage urgently as possible classic salt-wasting disease while endocrine evaluation proceeds. [8][23][24]" ], [ "Only mildly increased 17-hydroxyprogesterone or unclear diagnosis", "Screening and baseline testing may not distinguish 21-hydroxylase deficiency from other enzyme defects. [22][23]", "Perform cosyntropin stimulation with a complete adrenal steroid profile; consider genotyping. [22][23][24]" ] ] } }, { "id": "biochemical-confirmation", "eyebrow": "Diagnostic testing", "heading": "Use timed 17-hydroxyprogesterone testing and reflex cosyntropin profiling", "intro": "Sampling conditions determine whether 17-hydroxyprogesterone is an effective diagnostic discriminator.", "paragraphs": [ "For symptomatic individuals past infancy, screen with baseline serum 17-hydroxyprogesterone collected before 8 AM and measured by liquid chromatography-tandem mass spectrometry. In menstruating patients, obtain the sample in the early follicular phase to reduce interpretive error from cycle-related steroid variation. [22]", "A borderline baseline 17-hydroxyprogesterone should trigger a cosyntropin stimulation test with a complete adrenocortical steroid profile rather than a diagnosis based on one indeterminate value. This approach distinguishes 21-hydroxylase deficiency from other steroidogenic enzyme defects. [22]", "A commonly used confirmatory protocol administers 250 micrograms of cosyntropin intravenously and measures serum 17-hydroxyprogesterone plus an adrenal steroid panel at baseline and 60 minutes. The stimulated panel is particularly important beyond the newborn period, when random 17-hydroxyprogesterone may be insufficiently elevated for accurate diagnosis of nonclassic disease. [24]", "When stimulated testing remains nondiagnostic, especially in a patient already receiving glucocorticoid therapy, obtain genotyping to clarify the diagnosis. In newborns, genotyping also helps interpret equivocal biochemical results and supports genetic counseling. [22][23]" ], "bullets": [ "Preferred outpatient screening specimen: serum before 8 AM, analyzed by LC-MS/MS. [22]", "Preferred timing in menstruating patients: early follicular phase. [22]", "Indication for cosyntropin testing: borderline baseline 17-hydroxyprogesterone or uncertainty among steroidogenic defects. [22]", "Escalate to genotyping when biochemical testing is equivocal or altered by glucocorticoid exposure. [22][23]" ], "subsections": [], "table": { "caption": "Testing strategy by clinical setting. [22][23][24]", "columns": [ "Clinical setting", "Initial test", "Interpretation and escalation" ], "rows": [ [ "Positive newborn screen", "Serum 17-hydroxyprogesterone, electrolytes, and plasma renin activity. [23]", "Confirm biochemical disease and identify salt-wasting risk; use cosyntropin testing if 17-hydroxyprogesterone elevation is mild or diagnosis is unclear. [22][23]" ], [ "Symptomatic patient past infancy", "Pre-8 AM serum 17-hydroxyprogesterone by LC-MS/MS. [22]", "If borderline, obtain cosyntropin-stimulated complete adrenocortical profile. [22]" ], [ "Persistent diagnostic uncertainty", "Cosyntropin test with baseline and 60-minute adrenal steroid measurements. [24]", "Use genotyping when stimulated findings are nondiagnostic, particularly during glucocorticoid therapy. [22]" ] ] } }, { "id": "differential-diagnosis", "eyebrow": "Etiologic discrimination", "heading": "Distinguish 21-hydroxylase deficiency from other steroidogenic disorders", "intro": "The adrenal steroid pattern, mineralocorticoid phenotype, and sex-steroid precursor profile direct the next diagnostic step.", "paragraphs": [ "21-Hydroxylase deficiency is caused by pathogenic variants in CYP21A2 and produces impaired cortisol synthesis, accumulation of precursors including 17-hydroxyprogesterone, increased ACTH drive, and shunting toward adrenal androgen production. The biochemical consequence is central to both newborn screening and targeted confirmatory testing. [9][23][24]", "A complete post-cosyntropin steroid profile is required when 17-hydroxyprogesterone is indeterminate because elevated precursor concentrations are not unique to 21-hydroxylase deficiency. The Endocrine Society recommends this strategy specifically to differentiate 21-hydroxylase deficiency from other enzyme defects. [22]", "Consider P450 oxidoreductase deficiency when genital or steroidogenic findings suggest congenital adrenal hyperplasia but electrolytes and mineralocorticoid function are normal, cortisol is nearly normal but has a poor ACTH-stimulated response, sex-steroid precursors are low, and progesterone and 17-hydroxyprogesterone have variable ACTH responses. This pattern should redirect testing toward comprehensive steroid profiling and genotype confirmation rather than assumed 21-hydroxylase deficiency. [24]" ], "bullets": [ "High 17-hydroxyprogesterone with androgen excess and cortisol deficiency supports 21-hydroxylase deficiency. [23][24]", "Normal mineralocorticoid function with low sex-steroid precursors favors P450 oxidoreductase deficiency over classic 21-hydroxylase deficiency. [24]", "Use genotype testing as a diagnostic complement when biochemical phenotype is equivocal. [22][23]" ], "subsections": [], "table": { "caption": "Steroidogenic patterns that alter the diagnostic pathway. [22][23][24]", "columns": [ "Pattern", "Diagnostic implication", "Next step" ], "rows": [ [ "High 17-hydroxyprogesterone with cortisol deficiency and androgen excess", "Compatible with 21-hydroxylase deficiency. [23][24]", "Define classic versus nonclassic phenotype and assess mineralocorticoid status with electrolytes and plasma renin activity when relevant. [23]" ], [ "Borderline 17-hydroxyprogesterone", "Does not reliably distinguish 21-hydroxylase deficiency from another enzyme defect. [22]", "Obtain cosyntropin-stimulated complete adrenocortical profile. [22]" ], [ "Normal electrolytes/mineralocorticoid function, low sex-steroid precursors, poor cortisol response to ACTH", "Suggests P450 oxidoreductase deficiency. [24]", "Use comprehensive steroid profiling and genotype-directed confirmation. [24]" ] ] } }, { "id": "management-and-monitoring", "eyebrow": "Longitudinal care", "heading": "Match therapy and surveillance to cortisol, mineralocorticoid, androgen, and reproductive consequences", "intro": "Management aims to replace deficient hormones without excess glucocorticoid exposure.", "paragraphs": [ "Glucocorticoid replacement is the foundational treatment for 21-hydroxylase deficiency because the disorder is characterized by impaired cortisol synthesis and ACTH-driven adrenal androgen excess. In classic disease, intercurrent illness requires glucocorticoid stress dosing; acute illness poses adrenal-crisis risk particularly in salt-wasting 21-hydroxylase deficiency. [1][8][11]", "For patients with classic salt-wasting disease who cannot take oral fludrocortisone, intravenous hydrocortisone at higher doses with sodium chloride can provide temporary mineralocorticoid effect; 20 mg hydrocortisone is described as equivalent to 0.1 mg 9-alpha-fludrocortisone. [11]", "Avoid chronic glucocorticoid overtreatment. Adult observational experience describes frequent obesity, adverse health metrics, reduced quality of life, and apparent glucocorticoid overtreatment; chronic therapy in women should use the minimum glucocorticoid amount that maintains an acceptable testosterone concentration, individualized to the patient. [10]", "In adult males, evaluate testicular masses or infertility with testicular ultrasonography because testicular adrenal rest tumors may be palpable or detectable only by ultrasound. These ACTH-responsive lesions can regress with adequate glucocorticoid therapy and ACTH suppression, whereas inadequate glucocorticoid control promotes growth. [9]", "For women pursuing pregnancy, optimize adrenal replacement before ovulation induction. A follicular-phase progesterone below 0.6 ng/mL (2 nmol/L) is associated with conception; described regimens include multiple daily hydrocortisone and/or prednisolone doses, with a 0.5 to 2 mg bedtime prednisolone dose used alongside daytime hydrocortisone or prednisolone. Ovulation induction may still be needed despite optimized replacement. [10]" ], "bullets": [ "Teach and implement illness-related glucocorticoid stress dosing in classic disease. [11]", "Monitor for consequences of excess glucocorticoid exposure, including weight-related and quality-of-life burden. [10]", "Use testicular ultrasonography when male patients have suspected testicular adrenal rest tumors or infertility. [9]", "In women seeking conception, measure follicular-phase progesterone and intensify adrenal suppression when it remains at or above 0.6 ng/mL. [10]" ], "subsections": [ { "heading": "Emerging ACTH-directed therapy", "paragraphs": [ "Crinecerfont has been evaluated in a phase 3 trial in adults with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, a population conventionally treated with glucocorticoid replacement. Its role should be considered within specialty-directed management rather than as a substitute for urgent glucocorticoid replacement in cortisol-deficient disease. [1]" ], "bullets": [] } ], "table": { "caption": "Selected longitudinal management decisions in 21-hydroxylase deficiency. [9][10][11]", "columns": [ "Clinical problem", "Assessment", "Management implication" ], "rows": [ [ "Intercurrent illness in classic disease", "Assess need for glucocorticoid stress dosing and adrenal-crisis prevention. [11]", "Provide stress-dose glucocorticoid management; salt-wasting disease has greater adrenal-crisis risk than 11-beta-hydroxylase deficiency. [11]" ], [ "Inability to take oral fludrocortisone", "Assess need for temporary mineralocorticoid coverage. [11]", "Use higher-dose IV hydrocortisone with sodium chloride; 20 mg hydrocortisone provides mineralocorticoid activity equivalent to 0.1 mg 9-alpha-fludrocortisone. [11]" ], [ "Male infertility or testicular lesion", "Testicular ultrasonography for testicular adrenal rest tumor. [9]", "Optimize glucocorticoid therapy and ACTH suppression because these lesions may regress. [9]" ], [ "Pregnancy planning", "Measure follicular-phase progesterone. [10]", "Target progesterone below 0.6 ng/mL (2 nmol/L) with individualized hydrocortisone/prednisolone therapy; consider standard ovulation induction if needed. [10]" ] ] } }, { "id": "genetics-and-family-planning", "eyebrow": "Counseling", "heading": "Use genotyping when it changes diagnosis, counseling, or reproductive planning", "intro": "Genetic confirmation is most useful when biochemical results are equivocal or family risk requires clarification.", "paragraphs": [ "21-Hydroxylase deficiency is an autosomal recessive disorder associated with pathogenic CYP21A2 variants. Use genotyping as a complement to biochemical testing when neonatal or stimulated steroid findings are equivocal and when genotype clarification will inform family counseling. [9][23][24]", "Prenatal treatment considerations require specialized expertise because affected female fetuses can undergo virilization from prenatal androgen excess. Establishing the familial molecular diagnosis is therefore clinically relevant before reproductive counseling or any prenatal management discussion. [13][24]" ], "bullets": [ "Offer genetics-focused counseling after diagnostic confirmation because 21-hydroxylase deficiency is autosomal recessive. [9][13]", "Use genotyping to resolve equivocal biochemical testing and support counseling after a positive newborn screen. [22][23]" ], "subsections": [], "table": { "caption": "Situations in which CYP21A2 genotyping adds clinical value. [22][23]", "columns": [ "Situation", "Why genotype testing helps" ], "rows": [ [ "Equivocal newborn biochemical findings", "It complements 17-hydroxyprogesterone testing and aids interpretation after newborn screening. [23]" ], [ "Nondiagnostic cosyntropin-stimulated results", "It may confirm the diagnosis, particularly when glucocorticoid treatment complicates biochemical interpretation. [22]" ], [ "Family counseling and reproductive planning", "It identifies the molecular basis of an autosomal recessive condition for familial risk assessment. [9][13]" ] ] } } ], "faq": [], "references": [ { "number": 1, "title": "Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal ...", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMoa2404656", "authors": "www.nejm.org", "host": "www.nejm.org" }, { "number": 2, "title": "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase ...", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/pdf/10.1056/NEJM199012273232605", "authors": "www.nejm.org", "host": "www.nejm.org" }, { "number": 3, "title": "Adrenomedullary Dysplasia and Hypofunction in Patients ...", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/full/10.1056/NEJM200011093431903", "authors": "www.nejm.org", "host": "www.nejm.org" }, { "number": 4, "title": "Congenital Adrenal Hyperplasia", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMra021561", "authors": "www.nejm.org", "host": "www.nejm.org" }, { "number": 5, "title": "“Nonfunctional” Adrenal Tumors and the Risk for Incident ...", "detail": "www.acpjournals.org", "url": "https://www.acpjournals.org/doi/10.7326/M16-0547", "authors": "www.acpjournals.org", "host": "www.acpjournals.org" }, { "number": 6, "title": "Future Directions in the Study and Management of ...", "detail": "www.acpjournals.org", "url": "https://www.acpjournals.org/doi/10.7326/0003-4819-136-4-200202190-00012", "authors": "www.acpjournals.org", "host": "www.acpjournals.org" }, { "number": 7, "title": "Inherited Forms of Mineralocorticoid Hypertension", "detail": "www.ahajournals.org", "url": "https://www.ahajournals.org/doi/10.1161/01.HYP.28.6.927", "authors": "www.ahajournals.org", "host": "www.ahajournals.org" }, { "number": 8, "title": "Contemporary global management of 21-hydroxylase... : European Journal of Endocrinology", "detail": "journals.lww.com", "url": "https://journals.lww.com/00023063-202602000-00005", "authors": "journals.lww.com", "host": "journals.lww.com" }, { "number": 9, "title": "Hypogonadism - an overview | ScienceDirect Topics", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/hypogonadism", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com" }, { "number": 10, "title": "Adrenal Crisis - an overview", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/adrenal-crisis", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com" }, { "number": 11, "title": "Hydrocortisone Release - an overview", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/immunology-and-microbiology/hydrocortisone-release", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com" }, { "number": 12, "title": "11-Ketotestosterone - an overview", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/neuroscience/11-ketotestosterone", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com" }, { "number": 13, "title": "Prenatal Treatment of Congenital Adrenal Hyperplasia ...", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/10.1007/s10897-012-9508-8", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com" }, { "number": 14, "title": "Long‐term health consequences of congenital adrenal ...", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/full/10.1111/cen.14967", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com" }, { "number": 15, "title": "21‐Hydroxylase Deficiency - NEWFIELD - 1997", "detail": "nyaspubs.onlinelibrary.wiley.com", "url": "https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1997.tb52145.x", "authors": "nyaspubs.onlinelibrary.wiley.com", "host": "nyaspubs.onlinelibrary.wiley.com" }, { "number": 16, "title": "Glucocorticoid replacement regimens for treating ...", "detail": "www.cochranelibrary.com", "url": "https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012517.pub2/references", "authors": "www.cochranelibrary.com", "host": "www.cochranelibrary.com" }, { "number": 17, "title": "Adrenal Insufficiency: Still a Cause of Morbidity and Death ...", "detail": "pediatrics.aappublications.org", "url": "https://pediatrics.aappublications.org/content/119/2/e484", "authors": "pediatrics.aappublications.org", "host": "pediatrics.aappublications.org" }, { "number": 18, "title": "Term Infant With Ambiguous Genitalia | NeoReviews", "detail": "neoreviews.aappublications.org", "url": "https://neoreviews.aappublications.org/content/14/10/e539", "authors": "neoreviews.aappublications.org", "host": "neoreviews.aappublications.org" }, { "number": 19, "title": "Adrenal Insufficiency | Pediatrics In Review", "detail": "pedsinreview.aappublications.org", "url": "https://pedsinreview.aappublications.org/content/36/3/92", "authors": "pedsinreview.aappublications.org", "host": "pedsinreview.aappublications.org" }, { "number": 20, "title": "Primary adrenal insufficiency in adults: When to suspect, how to diagnose and manage | Cleveland Clinic Journal of medicine", "detail": "www.ccjm.org", "url": "https://www.ccjm.org/content/91/9/553", "authors": "www.ccjm.org", "host": "www.ccjm.org" }, { "number": 21, "title": "Evaluation, Treatment, and Prevention of Vitamin D Deficiency", "detail": "www.ccjm.org", "url": "https://www.ccjm.org/lookup/external-ref?access_num=10.1210%2Fjc.2011-0385&link_type=DOI", "authors": "www.ccjm.org", "host": "www.ccjm.org" }, { "number": 22, "title": "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6456929", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov" }, { "number": 23, "title": "Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7569755", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov" }, { "number": 24, "title": "Congenital Adrenal Hyperplasia - Endotext - NCBI Bookshelf", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/books/NBK278953", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov" } ], "editorialNote": "Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.", "citations": [ { "number": 1, "title": "Phase 3 Trial of Crinecerfont in Adult Congenital Adrenal ...", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMoa2404656", "authors": "www.nejm.org", "host": "www.nejm.org", "snippet": "by RJ Auchus · 2024 · Cited by 86 — 21-hydroxylase deficiency congenital adrenal hyperplasia (CAH) is treated with glucocorticoid replacement therapy.", "score": 0.6426349 }, { "number": 2, "title": "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase ...", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/pdf/10.1056/NEJM199012273232605", "authors": "www.nejm.org", "host": "www.nejm.org", "snippet": "by GB Cutler Jr · 1990 · Cited by 128 — 21- hydroxylase deficiency results in increased production of adrenal androgens and decreased production of glucocorticoids and", "score": 0.6342494 }, { "number": 3, "title": "Adrenomedullary Dysplasia and Hypofunction in Patients ...", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/full/10.1056/NEJM200011093431903", "authors": "www.nejm.org", "host": "www.nejm.org", "snippet": "by DP Merke · 2000 · Cited by 329 — The most common cause of congenital adrenal hyperplasia is 21-hydroxylase deficiency, with an incidence of approximately 1 case per 15,000 live", "score": 0.6216563 }, { "number": 4, "title": "Congenital Adrenal Hyperplasia", "detail": "www.nejm.org", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMra021561", "authors": "www.nejm.org", "host": "www.nejm.org", "snippet": "by PW Speiser · 2003 · Cited by 1337 — The most frequent is steroid 21-hydroxylase deficiency, accounting for more than 90 percent of cases. This article discusses the molecular mechanisms,", "score": 0.572078 }, { "number": 5, "title": "“Nonfunctional” Adrenal Tumors and the Risk for Incident ...", "detail": "www.acpjournals.org", "url": "https://www.acpjournals.org/doi/10.7326/M16-0547", "authors": "www.acpjournals.org", "host": "www.acpjournals.org", "snippet": "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline.", "score": 0.7817479 }, { "number": 6, "title": "Future Directions in the Study and Management of ...", "detail": "www.acpjournals.org", "url": "https://www.acpjournals.org/doi/10.7326/0003-4819-136-4-200202190-00012", "authors": "www.acpjournals.org", "host": "www.acpjournals.org", "snippet": "by DP Merke · 2002 · Cited by 235 — 21-Hydroxylase deficiency is responsible for more than 95% of cases and is one of the most common known autosomal recessive disorders.", "score": 0.46293488 }, { "number": 7, "title": "Inherited Forms of Mineralocorticoid Hypertension", "detail": "www.ahajournals.org", "url": "https://www.ahajournals.org/doi/10.1161/01.HYP.28.6.927", "authors": "www.ahajournals.org", "host": "www.ahajournals.org", "snippet": "by PC White · 1996 · Cited by 117 — More than 90% of cases are caused by 21-hydroxylase deficiency. This usually affects both aldosterone and cortisol biosynthesis, leading to signs of", "score": 0.33424217 }, { "number": 8, "title": "Contemporary global management of 21-hydroxylase... : European Journal of Endocrinology", "detail": "journals.lww.com", "url": "https://journals.lww.com/00023063-202602000-00005", "authors": "journals.lww.com", "host": "journals.lww.com", "snippet": "Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is the commonest genetic cause of adrenal insufficiency. Although guidelines for CAH management exist, their implementation and impact on quality of care remain unclear due to limited standardization in monitoring and benchmarking", "score": 0.7999589 }, { "number": 9, "title": "Hypogonadism - an overview | ScienceDirect Topics", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/hypogonadism", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "21-Hydroxylase deficiency is an autosomal recessive condition caused by a mutation in the _CYP21_ gene. It is the most common enzymatic defect causing con­genital adrenal hyperplasia. 21-Hydroxylase deficiency produces an accumulation of steroid substrates (17-hydroxyprogesterone and progesterone) t", "score": 0.67166495 }, { "number": 10, "title": "Adrenal Crisis - an overview", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/adrenal-crisis", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "##### Congenital Adrenal Hyperplasia (CAH): 21-Hydroxylase Deficiency [...] Little data exist to guide the optimal management of adults with 21OHD, either for long-term glucocorticoid replacement or for improving fertility.85 A range of treatment regimens are used without obvious rationale, although", "score": 0.66699636 }, { "number": 11, "title": "Hydrocortisone Release - an overview", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/immunology-and-microbiology/hydrocortisone-release", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "From HowStuffWorks 2001 © and Wendelaar Bonga SE (1997) The stress response in fish. _Physiological Reviews_ 77: 591–625.\n\nShow more\n\nView chapterExplore book\n\nRead full chapter\n\nURL:\n\nReference workImage 6: Encyclopedia of Fish Physiology 2011, Encyclopedia of Fish PhysiologyP. Kiilerich, P. Prunet", "score": 0.63125396 }, { "number": 12, "title": "11-Ketotestosterone - an overview", "detail": "www.sciencedirect.com", "url": "https://www.sciencedirect.com/topics/neuroscience/11-ketotestosterone", "authors": "www.sciencedirect.com", "host": "www.sciencedirect.com", "snippet": "Glucocorticoid therapy for women with classic 21-hydroxylase deficiency (21OHD) seeking pregnancy should be titrated to achieve a follicular-phase. Congenital", "score": 0.57437146 }, { "number": 13, "title": "Prenatal Treatment of Congenital Adrenal Hyperplasia ...", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/10.1007/s10897-012-9508-8", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com", "snippet": "Congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency is a common autosomal recessive disorder due to mutations in", "score": 0.61168414 }, { "number": 14, "title": "Long‐term health consequences of congenital adrenal ...", "detail": "onlinelibrary.wiley.com", "url": "https://onlinelibrary.wiley.com/doi/full/10.1111/cen.14967", "authors": "onlinelibrary.wiley.com", "host": "onlinelibrary.wiley.com", "snippet": "by R Pofi · 2024 · Cited by 44 — Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency accounts for 95% of all CAH cases and is one of the most common", "score": 0.57666177 }, { "number": 15, "title": "21‐Hydroxylase Deficiency - NEWFIELD - 1997", "detail": "nyaspubs.onlinelibrary.wiley.com", "url": "https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1997.tb52145.x", "authors": "nyaspubs.onlinelibrary.wiley.com", "host": "nyaspubs.onlinelibrary.wiley.com", "snippet": "Over 90% of CAH cases are caused by 21-hydroxylase deficiency (less frequent causes are 11β-hydroxylase deficiency and 3β-hydroxysteroid", "score": 0.5272928 }, { "number": 16, "title": "Glucocorticoid replacement regimens for treating ...", "detail": "www.cochranelibrary.com", "url": "https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012517.pub2/references", "authors": "www.cochranelibrary.com", "host": "www.cochranelibrary.com", "snippet": "Recent advances in diagnosis, treatment, and outcome of congenital adrenal hyperplasia due to 21‐hydroxylase deficiency. Reviews in Endocrine and Metabolic", "score": 0.6852132 }, { "number": 17, "title": "Adrenal Insufficiency: Still a Cause of Morbidity and Death ...", "detail": "pediatrics.aappublications.org", "url": "https://pediatrics.aappublications.org/content/119/2/e484", "authors": "pediatrics.aappublications.org", "host": "pediatrics.aappublications.org", "snippet": "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Lessons from 30 years of clinical diagnosis and treatment of congenital", "score": 0.67321366 }, { "number": 18, "title": "Term Infant With Ambiguous Genitalia | NeoReviews", "detail": "neoreviews.aappublications.org", "url": "https://neoreviews.aappublications.org/content/14/10/e539", "authors": "neoreviews.aappublications.org", "host": "neoreviews.aappublications.org", "snippet": "21-OH deficiency is the most common cause of CAH. 21-OH deficiency leads to absent or low levels of cortisol, Congenital adrenal hyperplasia (", "score": 0.6350646 }, { "number": 19, "title": "Adrenal Insufficiency | Pediatrics In Review", "detail": "pedsinreview.aappublications.org", "url": "https://pedsinreview.aappublications.org/content/36/3/92", "authors": "pedsinreview.aappublications.org", "host": "pedsinreview.aappublications.org", "snippet": "To determine a possible autoimmune cause, serum antibodies against 21-hydroxylase enzyme should be measured in all patients past infancy.", "score": 0.5253938 }, { "number": 20, "title": "Primary adrenal insufficiency in adults: When to suspect, how to diagnose and manage | Cleveland Clinic Journal of medicine", "detail": "www.ccjm.org", "url": "https://www.ccjm.org/content/91/9/553", "authors": "www.ccjm.org", "host": "www.ccjm.org", "snippet": "21-Hydroxylase antibody testing. Since most cases are autoimmune, the recommended workup begins with 21-hydroxylase antibodies. Imaging is not necessary and is relatively nonspecific for a diagnosis of autoimmune primary adrenal insufficiency but may show small atrophic adrenal glands. [...] When au", "score": 0.334503 }, { "number": 21, "title": "Evaluation, Treatment, and Prevention of Vitamin D Deficiency", "detail": "www.ccjm.org", "url": "https://www.ccjm.org/lookup/external-ref?access_num=10.1210%2Fjc.2011-0385&link_type=DOI", "authors": "www.ccjm.org", "host": "www.ccjm.org", "snippet": "by MF Holick · 2011 · Cited by 15629 — The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emp.", "score": 0.05576667 }, { "number": 22, "title": "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6456929", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "### Diagnosis of congenital adrenal hyperplasia\n\n 3.1 In infants with positive newborn screens for congenital adrenal hyperplasia we recommend referral to pediatric endocrinologists (if regionally available) and evaluation by cosyntropin stimulation testing as needed. (1|⊕⊕⊕○)\n\n 3.2 In symptomat", "score": 0.8437023 }, { "number": 23, "title": "Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy", "detail": "pmc.ncbi.nlm.nih.gov", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7569755", "authors": "pmc.ncbi.nlm.nih.gov", "host": "pmc.ncbi.nlm.nih.gov", "snippet": "### 2.4. Diagnosis and Treatment\n\nInfants with newborn screen results suggestive of 21OHD should be referred to and assessed by a pediatric endocrinologist. Elevated serum 17OHP levels can confirm 21OHD, and measurement of serum electrolytes and plasma renin activity identify newborns at risk of a s", "score": 0.8252664 }, { "number": 24, "title": "Congenital Adrenal Hyperplasia - Endotext - NCBI Bookshelf", "detail": "www.ncbi.nlm.nih.gov", "url": "https://www.ncbi.nlm.nih.gov/books/NBK278953", "authors": "www.ncbi.nlm.nih.gov", "host": "www.ncbi.nlm.nih.gov", "snippet": "Confirmatory testing is often performed with the cosyntropin (ACTH 1-24) stimulation test (250 μg cosyntropin intravenously), measuring serum levels of 17OHP and a panel of adrenal steroids at baseline and 60 min. A nomogram (Figure 8) has been developed to describe 21OHD severity (160). Stimulation", "score": 0.8124067 } ], "publishedAt": "2026-08-24T18:27:49.096045+00:00", "updatedAt": "2026-08-24T18:27:49.096045+00:00", "readingMinutes": 5, "slug": "21-hydroxylase-deficiency" }