Table of ContentsView AllTable of ContentsCausesSymptomsDiagnosisTreatment
Table of ContentsView All
View All
Table of Contents
Causes
Symptoms
Diagnosis
Treatment
LOCAH is a milder form of “classic” congenital adrenal hyperplasia (CAH) with symptoms typically developing during puberty or early adulthood. The treatment differs from classic CAH and may involveoral hormonal contraceptivesorandrogen blockers.
This article describes the causes and symptoms of late-onset congenital adrenal hyperplasia, including the pattern of inheritance from parents to child. It also explains how LOCAH is diagnosed and treated.
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What Causes Late-Onset Congenital Adrenal Hyperplasia?
One of the consequences of decreased cortisol production is the increased production of androgens, most notablytestosterone.The increase in androgens, known ashyperandrogenism, accounts for the characteristic symptoms of LOCAH.
Where LOCAH differs from classic CAH is that cortisol production is only mildly suppressed and the symptoms are not seen during infancy (as it is with CAH) but in later childhood or early adulthood.
How Common Is LOCAH?In addition to being milder than classic CAH, LOCAH is more common, affecting one of every 200 children born in the United States. People of Ashkenazi Jewish, Hispanic, Mediterranean, Middle Eastern, and Alaskan Eskimo descent are most affected. (In contrast, classic CAH occurs in roughly one of every 14,000 children.)
How Common Is LOCAH?
In addition to being milder than classic CAH, LOCAH is more common, affecting one of every 200 children born in the United States. People of Ashkenazi Jewish, Hispanic, Mediterranean, Middle Eastern, and Alaskan Eskimo descent are most affected. (In contrast, classic CAH occurs in roughly one of every 14,000 children.)
Pattern of Inheritance
TheCYP21A2mutation is passed from parents to children in anautosomal recessive pattern. What this means is the disease will only occur if both parents carry theCYP21A2mutation and each passes one copy of the mutation to their child. If only one copy is passed, the child will be a “carrier” without any symptoms.
Statistically, if both parents are carriers of theCYP21A2gene, the odds of their child developing LOCAH is 25%.
Symptoms of Late-Onset Congenital Adrenal Hyperplasia
The symptoms of LOCAH correspond to increases in testosterone above what would normally occur. Even so, the increases are not always significant and many people with LOCAH can be entirelyasymptomatic(without symptoms). This is especially true with males.
However, some variations of theCYP21A2gene mutation are associated with severe 21-hydroxylase deficiency and high increases in testosterone production, resulting in overt and potentially distressing symptoms.
Symptoms in Females
Symptoms of LOCAH tend to be more profound in females because steep elevations in testosterone, while generally well tolerated in males, can be problematic in females during puberty and later life.
One of the earliest possible signs in females during puberty ispremature pubarche. This is the term that describes sexual maturation that occurs well before what would normally be expected.
While females will experience a testosterone surge during puberty in the same way as males, the excessive output can cause the early development of breasts, pubic hair, and other secondary female sex characteristics. Cases of premature pubarche have been reported in girls as young as 6 months with the development of pubic hair.
High testosterone levels can also lead tochronic acneduring puberty and well into adulthood.
After puberty, the effects of LOCAH can even be more problematic in some females, manifesting with symptoms of hyperandrogenism, such as:
The symptoms are similar to those ofpolycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism in females. What differentiates the two is the absence ofovarian cystswith LOCAH. Beyond this, LOCAH and PCOS can be difficult to distinguish without blood tests.
Symptoms in Males
The symptoms of LOCAH in males are often indistinguishable from what is seen in males without LOCAH.At the same, elevations in testosterone may not be high enough to cause any notable physiological changes, other than perhaps a higher risk of chronic acne.
In later life, LOCAH can also be symptomatic. If symptoms were to occur, they might regarded as normal or attributed to other causes.
Possible symptoms of LOCAH in males include:
How Is Late-Onset Congenital Adrenal Hyperplasia Diagnosed?
Because LOCAH is milder than classic CAH with fewer overt symptoms, it can often go diagnosed. In fact, some studies suggest that up to 90% of females with LOCAH remain undiagnosed.
If LOCAH is suspected, the diagnosis would involve a review of your medical history, a physical exam, and blood tests to check for hormonal imbalances.
Blood tests commonly used to diagnose LOCAH include:
The ACTH stimulation test remains the gold standard for diagnosing congenital adrenal hyperplasia in all of its forms.
The ACTH stimulation tests can also differentiate LOCAH from PCOS as females with PCOS often have normal adrenal gland function. If ACHT is administered, females with PCOS will experience a rise in 17-OHP levels whereas those with LOCAH will not.
How Is Late-Onset Adrenal Hyperplasia Treated?
LOCAH is not a potentially life-threatening condition like classic CAH can be and doesn’t need to be treated if doesn’t cause any symptoms.Even if treatment is needed, LOCAH is not treated in the same way as classic CAH.
With classic CAH,glucocorticoid (steroid) drugsare used as a substitute for cortisol to help bring down testosterone levels. With LOCAH, the risk of glucocorticoids (including the risk of gastric ulcers and bleeding) outweighs any potential benefit.
For females with symptomatic LOCAH, treatment may involve oral medications that counter the effects of high testosterone directly, including:
A newer drug calledcrinecerfontis under investigation for children and adolescents with classic CAH. It may have an application with LOCAH as well as it is not a glucocorticoid and has few serious side effects. Side effects tend to be mild and mostly involve headaches, runny nose, sneezing, nasal congestion, and vomiting.
Summary
Symptoms of LOCAH include early sexual maturation, acne, male pattern hair loss, abnormal facial or body hair, irregular periods, and infertility. Many people have no symptoms.
LOCAH can be diagnosed with blood tests. If needed, females can be treated with birth control pills or androgen blockers to counter the effects of high testosterone.
7 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Adriaansen BP, Schröder MA, Span PN, Sweep FC, van Herwaarden AE, Claahsen-van der Grinten HL.Challenges in treatment of patients with non-classic congenital adrenal hyperplasia.Front Endocrinol (Lausanne).2022:13:1064024. doi:10.3389/fendo.2022.1064024Jha S, Turcu AF.Non-classic congenital adrenal hyperplasia: what do endocrinologists need to know?Endocrinol Metab Clin North Am.2021 Mar;50(1):151–165. doi:10.1016/j.ecl.2020.10.008Yau M, Gujral J, New MI.Clinical recognition. In:Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment. South Dartmouth, MA: MDText.com, Inc.; 2024.Masiutin MG, Yadav MK.Letter to the editor regarding the article “Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome”.Urology. 2022;169: 273. doi:10.1016/j.urology.2022.07.051Merke DP, Auchus RJ.Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.New England J Med.2020:383(13):1248–1261. doi:10.1056/NEJMra1909786Papadakis G, Kandraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E.Polycystic ovary syndrome and NC-CAH: distinct characteristics and common findings. a systematic review.Front Endocrinol (Lausanne).2019;10:388. doi:10.3389/fendo.2019.00388Newfield RS, Sarafoglu K, Fechner PY, et al.Crinecerfont, a CRF1 receptor antagonist, lowers adrenal androgens in adolescents with congenital adrenal hyperplasia.J Clin Endocrinol Metab. 2023 Oct 18;108(11):2871-2878. doi:10.1210/clinem/dgad270
7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Adriaansen BP, Schröder MA, Span PN, Sweep FC, van Herwaarden AE, Claahsen-van der Grinten HL.Challenges in treatment of patients with non-classic congenital adrenal hyperplasia.Front Endocrinol (Lausanne).2022:13:1064024. doi:10.3389/fendo.2022.1064024Jha S, Turcu AF.Non-classic congenital adrenal hyperplasia: what do endocrinologists need to know?Endocrinol Metab Clin North Am.2021 Mar;50(1):151–165. doi:10.1016/j.ecl.2020.10.008Yau M, Gujral J, New MI.Clinical recognition. In:Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment. South Dartmouth, MA: MDText.com, Inc.; 2024.Masiutin MG, Yadav MK.Letter to the editor regarding the article “Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome”.Urology. 2022;169: 273. doi:10.1016/j.urology.2022.07.051Merke DP, Auchus RJ.Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.New England J Med.2020:383(13):1248–1261. doi:10.1056/NEJMra1909786Papadakis G, Kandraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E.Polycystic ovary syndrome and NC-CAH: distinct characteristics and common findings. a systematic review.Front Endocrinol (Lausanne).2019;10:388. doi:10.3389/fendo.2019.00388Newfield RS, Sarafoglu K, Fechner PY, et al.Crinecerfont, a CRF1 receptor antagonist, lowers adrenal androgens in adolescents with congenital adrenal hyperplasia.J Clin Endocrinol Metab. 2023 Oct 18;108(11):2871-2878. doi:10.1210/clinem/dgad270
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Adriaansen BP, Schröder MA, Span PN, Sweep FC, van Herwaarden AE, Claahsen-van der Grinten HL.Challenges in treatment of patients with non-classic congenital adrenal hyperplasia.Front Endocrinol (Lausanne).2022:13:1064024. doi:10.3389/fendo.2022.1064024Jha S, Turcu AF.Non-classic congenital adrenal hyperplasia: what do endocrinologists need to know?Endocrinol Metab Clin North Am.2021 Mar;50(1):151–165. doi:10.1016/j.ecl.2020.10.008Yau M, Gujral J, New MI.Clinical recognition. In:Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment. South Dartmouth, MA: MDText.com, Inc.; 2024.Masiutin MG, Yadav MK.Letter to the editor regarding the article “Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome”.Urology. 2022;169: 273. doi:10.1016/j.urology.2022.07.051Merke DP, Auchus RJ.Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.New England J Med.2020:383(13):1248–1261. doi:10.1056/NEJMra1909786Papadakis G, Kandraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E.Polycystic ovary syndrome and NC-CAH: distinct characteristics and common findings. a systematic review.Front Endocrinol (Lausanne).2019;10:388. doi:10.3389/fendo.2019.00388Newfield RS, Sarafoglu K, Fechner PY, et al.Crinecerfont, a CRF1 receptor antagonist, lowers adrenal androgens in adolescents with congenital adrenal hyperplasia.J Clin Endocrinol Metab. 2023 Oct 18;108(11):2871-2878. doi:10.1210/clinem/dgad270
Adriaansen BP, Schröder MA, Span PN, Sweep FC, van Herwaarden AE, Claahsen-van der Grinten HL.Challenges in treatment of patients with non-classic congenital adrenal hyperplasia.Front Endocrinol (Lausanne).2022:13:1064024. doi:10.3389/fendo.2022.1064024
Jha S, Turcu AF.Non-classic congenital adrenal hyperplasia: what do endocrinologists need to know?Endocrinol Metab Clin North Am.2021 Mar;50(1):151–165. doi:10.1016/j.ecl.2020.10.008
Yau M, Gujral J, New MI.Clinical recognition. In:Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment. South Dartmouth, MA: MDText.com, Inc.; 2024.
Masiutin MG, Yadav MK.Letter to the editor regarding the article “Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome”.Urology. 2022;169: 273. doi:10.1016/j.urology.2022.07.051
Merke DP, Auchus RJ.Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.New England J Med.2020:383(13):1248–1261. doi:10.1056/NEJMra1909786
Papadakis G, Kandraki EA, Tseniklidi E, Papalou O, Diamanti-Kandarakis E.Polycystic ovary syndrome and NC-CAH: distinct characteristics and common findings. a systematic review.Front Endocrinol (Lausanne).2019;10:388. doi:10.3389/fendo.2019.00388
Newfield RS, Sarafoglu K, Fechner PY, et al.Crinecerfont, a CRF1 receptor antagonist, lowers adrenal androgens in adolescents with congenital adrenal hyperplasia.J Clin Endocrinol Metab. 2023 Oct 18;108(11):2871-2878. doi:10.1210/clinem/dgad270
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