Congenital Adrenal Hyperplasia

In a newborn with a positive screen, markedly elevated 17-hydroxyprogesterone (17-OHP), ambiguous genitalia, dehydration, vomiting, poor feeding, or clinical deterioration, obtain serum electrolytes and serum 17-OHP urgently. Mild screen elevations may be managed initially with a repeat filter-paper specimen, but marked elevation or concern for instability requires urgent assessment. PubMedPubMedCongenital adrenal hyperplasia: an update in children

Do not allow cosyntropin stimulation testing to delay treatment when CAH with adrenal insufficiency is clinically suspected. Salt-wasting classic 21-hydroxylase deficiency impairs aldosterone synthesis as well as cortisol synthesis, making intercurrent dehydration and physiologic stress clinically hazardous. PubMed+1PubMedCongenital adrenal hyperplasia: an update in childrenPubMedCongenital Adrenal Hyperplasia - Endotext - NCBI Bookshelf

After infancy, prioritize an early-morning baseline serum 17-OHP in patients with otherwise unexplained androgen excess or suspected nonclassic disease. A normal newborn screen does not exclude later recognition of CAH, and biochemical confirmation should precede long-term labeling or treatment when the patient is stable. PubMed+2PubMedCongenital adrenal hyperplasia: an update in childrenPubMedAdrenal Steroidogenesis and Congenital Adrenal HyperplasiaPubMedScreening for non-classic congenital adrenal hyperplasia in women: New insights using different immunoassays

The diagnostic standard for 21-hydroxylase-deficient CAH is serum 17-OHP, commonly confirmed with cosyntropin stimulation. In a patient with a congruent phenotype and unequivocally high 17-OHP, stimulation testing is generally unnecessary; values greater than 10,000 ng/dL strongly favor classic CAH. Oxford Academic+2Oxford AcademicCongenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase ...PubMedCongenital adrenal hyperplasia: an update in childrenPubMedCongenital Adrenal Hyperplasia - StatPearls - NCBI Bookshelf - NIH

For values that do not establish classic disease, perform a complete adrenal steroid profile before and 60 minutes after 0.25 mg cosyntropin. The profile should include 17-OHP, progesterone, cortisol, deoxycorticosterone, 11-deoxycortisol, pregnenolone, 17-hydroxypregnenolone, DHEA, and androstenedione, allowing both confirmation of 21-hydroxylase deficiency and recognition of alternative enzyme blocks. PubMedPubMedCongenital Adrenal Hyperplasia - StatPearls - NCBI Bookshelf - NIH

For nonclassic 21-hydroxylase deficiency, current screening practice uses early-morning 17-OHP. A basal concentration of at least 6 nmol/L is an effective screening threshold, and a 60-minute 17-OHP concentration greater than 30 nmol/L after 250 mcg ACTH supports diagnosis. Thresholds originated largely from immunoassay data, so report the analytic method and avoid transferring assay-specific cutoffs without validation. PubMed+1PubMedScreening for Nonclassic Congenital Adrenal Hyperplasia in the Era of Liquid Chromatography-Tandem Mass Spectrometry - PMCPubMedScreening for non-classic congenital adrenal hyperplasia in women: New insights using different immunoassays

Although 21-hydroxylase deficiency accounts for 95% to 99% of CAH, pathogenic defects in 11β-hydroxylase, 17α-hydroxylase/17,20-lyase, 3β-hydroxysteroid dehydrogenase type 2, StAR, P450 side-chain cleavage enzyme, and P450 oxidoreductase can produce CAH phenotypes. An atypical steroid pattern should therefore redirect testing beyond CYP21A2 alone. Oxford Academic+1Oxford AcademicGenetics in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency and Clinical Implications | Journal of the Endocrine Society | Oxford AcademicendocrineGenetics in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency and Clinical Implications | Endocrine Society

Marked elevation of Δ5 steroids—pregnenolone, 17-hydroxypregnenolone, DHEA, and DHEAS—with an increased Δ5:Δ4 ratio relative to progesterone, 17-OHP, and androstenedione supports 3β-hydroxysteroid dehydrogenase type 2 deficiency. Obtain these analytes in the pre- and post-cosyntropin profile when 17-OHP is ambiguous or another enzyme defect is suspected. PubMedPubMedCongenital Adrenal Hyperplasia - StatPearls - NCBI Bookshelf - NIH

Use molecular testing after clinical and hormonal phenotyping when biochemical results are equivocal, when another steroidogenic defect is suspected, or for genetic counseling. CYP21A2 testing is technically challenging, and genotype predicts phenotype usefully but imperfectly; avoid using genotype alone to override the clinical phenotype. Oxford Academic+2Oxford AcademicCongenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice GuidelineendocrineGenetics in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency and Clinical Implications | Endocrine SocietyPubMed21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia - GeneReviews® - NCBI Bookshelf

For classic 21-hydroxylase-deficient CAH, use glucocorticoid replacement and mineralocorticoid replacement; infants additionally require sodium supplementation. This approach addresses the cortisol deficiency of all classic forms and the aldosterone deficiency of salt-wasting disease. Oxford Academic+2Oxford AcademicCongenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice GuidelinePubMedCongenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline - PubMedPubMedCongenital Adrenal Hyperplasia - Endotext - NCBI Bookshelf

Provide explicit stress-dose glucocorticoid instructions to patients with classic CAH and their caregivers. Febrile illness, vomiting or diarrhea with dehydration, major trauma, and procedures requiring general anesthesia are defined high-risk settings because they can precipitate adrenal crisis. PubMedPubMed21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia - GeneReviews® - NCBI Bookshelf

Avoid routine prenatal CAH treatment outside experimental protocols. The Endocrine Society guideline characterizes prenatal treatment as experimental, and this recommendation is particularly relevant when counseling families after identification of a familial CYP21A2 variant. Oxford Academic+1Oxford AcademicCongenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice GuidelinePubMedCongenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline - PubMed

Do not use adrenalectomy as routine management. The guideline suggests avoiding adrenalectomy and recommends against routine experimental therapies intended to promote growth or delay puberty. PubMedPubMedCongenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline - PubMed

Reserve CYP21A2 genotyping for equivocal diagnostic presentations and genetic counseling rather than using it as the initial substitute for clinical and hormonal evaluation. 21-hydroxylase deficiency is autosomal recessive, and pathogenic variation in CYP21A2 produces a spectrum from classic to nonclassic disease. Oxford Academic+2Oxford AcademicCongenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice GuidelineendocrineGenetics in Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency and Clinical Implications | Endocrine SocietyPubMedCongenital Adrenal Hyperplasia - Endotext - NCBI Bookshelf

For an affected individual considering pregnancy, offer molecular testing to the reproductive partner. If the partner is not a carrier, the risk of an affected child is substantially reduced; if the partner is heterozygous for a known pathogenic variant, the risk of an affected child is 50% in each pregnancy. PubMedPubMed21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia - GeneReviews® - NCBI Bookshelf

When familial variants are known, evaluate newborn siblings promptly with both serum 17-OHP and molecular testing rather than relying on population screening alone. This is particularly important because early recognition enables prompt glucocorticoid and mineralocorticoid treatment in classic disease. PubMed+1PubMedCongenital Adrenal Hyperplasia - Endotext - NCBI BookshelfPubMed21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia - GeneReviews® - NCBI Bookshelf