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MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency
Abstract
Non-classic congenital adrenal hyperplasia (NCAH) is a relatively common disorder regardless of ethnicity, but most cases are never diagnosed, especially in males. A baseline 17-hydroxyprogesterone measurement may be used for screening, but 17-hydroxyprogesterone measurement after ACTH stimulation is the gold standard. We advocate a CYP21A2 mutation analysis to verify the diagnosis, for genetic counselling and for better prognostic and treatment guidance. Most patients are diagnosed in adolescence and adult life with hirsutism, acne, a PCOS-like picture and fertility issues. Many men with NCAH never seek medical attention and escape diagnosis. Although treatment is somewhat controversial, an early diagnosis and start of treatment may have positive implications on growth and be relevant for preventing and ameliorating the symptoms and consequences of androgen excess that develop over time, including fertility issues. Long-term treatment with glucocorticoids will improve the androgen symptoms but may result in long-term complications, such as obesity, insulin resistance, hypertension, osteoporosis and fractures. The glucocorticoid doses should be kept low. However, complications seen in NCAH, assumed to be caused by the glucocorticoid treatment, may also be associated with long-term androgen exposure. Oral contraceptive pills are a common treatment option for young females with NCAH. Regular clinical monitoring to improve the clinical outcome is recommended. It is important to acknowledge that glucocorticoid treatment will lead to secondary cortisol insufficiency and the need for stress dosing. Studies focusing on the specific difficulties patients with NCAH face, both those with a late clinical diagnosis and those with a neonatal diagnosis obtained by screening, are warranted.
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In the citing paper
“Children with NC CAH can present with signs of increased adrenal androgen production such as premature pubarche, acne, mild hirsutism and menstrual disturbances that can progress over time (427),”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [427]
In the citing paper
“Typical symptoms in affected women are hirsutism, oligo-and amenorrhea, acne, alopecia and sub-or infertility (427).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [427]
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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
Self-citationCongenital adrenal hyperplasia
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Self-citationCalissendorff, J., Juhlin, C. C., Sundin, A., Bancos, I., & Falhammar, H. (2021) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(21)00178-9 · Cited by 117
Self-citationWhittle, E., & Falhammar, H. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00136 · Cited by 87
“To overcome this disparity, diurnal curves using dried blood spots measuring 17OHP can be used, but such curves are currently only available in a few centers [1, 7].”
BackgroundSelf-citationApproach to androgen excess in women: Clinical and biochemical insights
Cussen, L., McDonnell, T., Bennett, G., Thompson, C. J., Sherlock, M., & O’Reilly, M. (2022) · Clinical Endocrinology · doi:10.1111/cen.14710 · Cited by 92
“m) is the gold standard for confirmatory diagnosis.(71) The Endocrine Society Guidelines recommend a stimulated 17OHP cut‐off value of 30 nmol/L for NCCAH diagnosis.”
Background
Metadata
- Authors
- Nordenström, A., & Falhammar, H.
- Affiliations
- Karolinska University Hospital (SE)
- Corresponding author
- Nordenström, Anna
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-03
- Volume
- 180
- Issue
- 3
- Pages
- R127-R145
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2904713638
- Cited by
- 158
- References
- 166
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 22 · 2023: 30 · 2022: 27 · 2021: 25 · 2020: 20 · 2019: 9
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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
- non-classical congenital adrenal hyperplasia, 21-hydroxylase deficiency, 17-hydroxyprogesterone, ACTH stimulation test, hirsutism, hyperandrogenism, glucocorticoid therapy, glucocorticoid adverse effects, oral contraceptives, fertility, genetic counseling, screening
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